Nicotine’s Effects on the Brain & Body & How to Quit Smoking or Vaping

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.880 | I'm Andrew Huberman,

00:00:10.300 | and I'm a professor of neurobiology and ophthalmology

00:00:13.240 | at Stanford School of Medicine.

00:00:15.080 | Today, we are discussing nicotine.

00:00:17.200 | Nicotine is one of the most commonly consumed substances

00:00:19.840 | on the entire planet.

00:00:21.620 | There are literally billions of people

00:00:23.720 | that ingest nicotine on a daily basis.

00:00:26.640 | Most of those people consume nicotine via smoking

00:00:29.680 | and in particular, smoking tobacco.

00:00:31.880 | Tobacco contains nicotine,

00:00:33.400 | and it contains a bunch of other things as well,

00:00:35.920 | which we will talk about.

00:00:37.160 | And the burning of tobacco liberates nicotine

00:00:39.400 | and makes it accessible to the various cells

00:00:41.840 | and tissues of the body.

00:00:43.160 | But of course, there are other sources of nicotine as well.

00:00:45.700 | Some people consume nicotine through dip,

00:00:48.220 | that is placing tobacco on the inside of the lip

00:00:51.160 | or in the cheek.

00:00:52.840 | Some people consume nicotine via snuff,

00:00:55.440 | which is literally the shoving of tobacco leaves up

00:00:58.360 | the nostrils and allowing the tobacco to access

00:01:01.360 | the nervous system and other areas of the body

00:01:03.900 | by permeating into the mucosal membranes,

00:01:06.460 | as is the lining, the soft lining of the nasal passages.

00:01:09.840 | And of course, there are nicotine patches, nicotine gum,

00:01:12.680 | there's nicotine in pill form,

00:01:14.340 | there are toothpicks dipped in nicotine, et cetera.

00:01:17.160 | Today, we are going to separate our discussion of nicotine

00:01:19.860 | from a discussion of smoking and vaping

00:01:22.240 | and the other forms of delivery for nicotine.

00:01:24.520 | We will be talking about smoking and vaping

00:01:27.080 | and other routes of nicotine administration,

00:01:29.480 | both for sake of highlighting their detriments to health

00:01:33.800 | and believe it or not, in certain cases,

00:01:37.520 | keep in mind, very specific certain cases,

00:01:40.040 | the possible health benefits of delivering nicotine

00:01:43.040 | through specific modalities.

00:01:45.560 | It turns out those modalities do not include

00:01:48.240 | smoking cigarettes or vaping.

00:01:50.800 | And we are going to pay particular attention

00:01:52.880 | to vaping today because vaping use is on the rise,

00:01:56.320 | in particular in young people and vaping use

00:02:00.360 | and the fact that most tobacco that's consumed

00:02:03.640 | through vaping includes quite amount of nicotine

00:02:06.760 | has created a scenario where nicotine,

00:02:09.040 | because of its ability to change certain chemicals

00:02:11.500 | in the brain can actually lead to addiction

00:02:14.200 | for a number of other substances related to vaping

00:02:17.560 | and vaping associated behaviors.

00:02:19.520 | If all of that seems like a lot to get your arms

00:02:21.860 | and your mind around right here at the outset, don't worry,

00:02:24.640 | I'll walk you through this regardless of whether or not

00:02:27.200 | you have a background in biology or not.

00:02:28.920 | I promise that you'll come through the end of this episode

00:02:31.940 | with a deep understanding of how nicotine works

00:02:34.280 | in the brain and body, some of its benefits,

00:02:36.640 | some of its potential drawbacks,

00:02:38.280 | and you'll have clear optics as to why smoking and vaping

00:02:42.420 | and other forms of nicotine delivery have the effects

00:02:44.920 | that they do on your biology and psychology.

00:02:47.840 | I'm pleased to announce that the Huberman Lab podcast

00:02:49.720 | is now partnered with Momentus Supplements.

00:02:52.060 | We partnered with Momentus for several important reasons.

00:02:54.280 | First of all, they ship internationally

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00:02:59.440 | Second of all, and perhaps most important,

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00:03:21.180 | and that you can add things and remove things

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00:03:26.440 | If you'd like to see the supplements

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00:03:28.940 | you can go to livemomentus.com/huberman.

00:03:32.040 | There you'll see those supplements,

00:03:33.160 | and just keep in mind that we are constantly expanding

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00:03:39.280 | Again, that's livemomentus.com/huberman.

00:03:41.880 | Before we go any further,

00:03:42.920 | I just want to highlight a key takeaway

00:03:45.180 | from a previous episode, which is our episode on focus,

00:03:48.960 | and in fact was a toolkit for focus.

00:03:51.820 | So during the toolkit for focus episode,

00:03:53.580 | we talked about a large number of behavioral pharmacologic

00:03:55.920 | and other interventions that you can use

00:03:58.160 | to increase your level of concentration and focus

00:04:00.660 | for whatever purpose, cognitive endeavors,

00:04:03.020 | learning languages, focusing in school,

00:04:05.220 | on work, et cetera, or physical pursuits.

00:04:08.220 | Now, one of the key takeaways

00:04:10.000 | is that there are really two key protocols

00:04:13.520 | that I believe everyone should understand and know about

00:04:15.840 | and why they work, because they are so effective,

00:04:18.540 | and also because they dovetail nicely

00:04:20.780 | with some of the information

00:04:21.760 | that we're going to talk about today,

00:04:23.380 | which will explain why nicotine is so effective

00:04:26.160 | in increasing focus.

00:04:28.160 | And these two protocols are as follows.

00:04:30.620 | Data based on studies done in Wendy Suzuki's lab

00:04:33.760 | at New York University,

00:04:35.440 | and of course, Wendy was a guest on this podcast,

00:04:37.940 | so you can check out that episode if you like,

00:04:39.720 | but studies done in her laboratory point to the fact

00:04:42.520 | that a daily very brief, in fact, only 13-minute meditation,

00:04:47.040 | can vastly increase focus and focusability,

00:04:50.400 | not just immediately after the meditation practice,

00:04:53.560 | but at all other times as well.

00:04:55.640 | So again, this is a meditation practice done daily

00:04:58.580 | for just 13 minutes.

00:04:59.660 | It's a very simple meditation practice

00:05:01.180 | where one sits or lies down, closes your eyes,

00:05:04.460 | and directs your attention to a place

00:05:07.420 | just between your two eyes and right above it,

00:05:09.740 | so on your forehead, but just inside of that.

00:05:11.800 | And please understand

00:05:13.000 | that your brain does not have sensory receptors,

00:05:14.840 | so unlike focusing on your fingertips

00:05:16.700 | and the sensations there, if you focus on your brain,

00:05:19.540 | you can't actually sense anything in your brain

00:05:21.420 | except your thoughts.

00:05:22.260 | So the idea then is that you continually bring your focus

00:05:25.380 | back to that location just about an inch behind your forehead

00:05:29.380 | over and over again,

00:05:30.220 | and it's the refocusing of your attention to that location

00:05:33.340 | after it drifts that succeeds

00:05:35.420 | in increasing your focusability,

00:05:37.000 | again, not just during the meditation and afterward,

00:05:39.280 | but at other times as well.

00:05:40.900 | So this 13-minute-a-day meditation is exceedingly simple

00:05:43.660 | and exceedingly effective.

00:05:45.460 | It should be performed every day, but if you miss a day,

00:05:48.020 | just go back to doing it, don't despair too much,

00:05:50.400 | and you will see these positive effects save the data,

00:05:52.760 | also increase effects on mood

00:05:54.500 | and other positive aspects of mental health and performance.

00:05:57.340 | So that's the first tool in protocol.

00:05:59.140 | The second tool in protocol relates to the general,

00:06:01.840 | what I call the aero model of focus.

00:06:04.660 | This was a model that I created

00:06:06.060 | in order to simplify the vast amounts of data

00:06:08.340 | on focus and concentration and how they are created

00:06:11.060 | by the various chemical systems within your brain.

00:06:14.020 | We're going to hear a lot about these chemical systems,

00:06:15.880 | again, today in the context of nicotine,

00:06:17.420 | and they are as follows.

00:06:19.400 | You can think about focus on any goal or any endeavor

00:06:23.140 | as an aero, so just imagine an aero,

00:06:24.940 | which has an aero head and a shaft,

00:06:26.740 | and we'll add a third component to it in a moment.

00:06:29.820 | The head of the aero, meaning the direction of your focus,

00:06:32.680 | is largely set by acetylcholine,

00:06:35.140 | which is a chemical in the brain.

00:06:36.660 | The shaft of the aero is set by a chemical called adrenaline,

00:06:41.060 | also called epinephrine, those are the same thing.

00:06:43.420 | In the brain, typically it's referred to as epinephrine,

00:06:46.220 | and in the body, it's more commonly referred to

00:06:48.380 | as adrenaline, but those are the same neurochemical.

00:06:51.040 | Epinephrine/adrenaline represents the shaft of the aero,

00:06:55.060 | and it's providing the energy for which to focus.

00:06:59.180 | And then we can put behind that aero a little propeller

00:07:01.660 | or a motor, if you like, and the propeller or motor

00:07:04.320 | in the context of this neurochemistry model is dopamine,

00:07:07.420 | which provides ongoing motivation.

00:07:09.140 | It pushes that aero forward continually

00:07:11.640 | as you strive to focus on a particular thing.

00:07:15.140 | This particular aero model,

00:07:16.700 | that is your ability to increase your focus,

00:07:19.620 | can be enhanced therefore by increasing acetylcholine,

00:07:23.060 | epinephrine, and dopamine simultaneously.

00:07:26.660 | And there are a lot of different ways to do that,

00:07:28.360 | but one of the more effective ways to do that

00:07:30.380 | via supplement protocols is so-called alpha-GPC.

00:07:34.160 | Alpha-GPC taken in 300 milligram form,

00:07:37.780 | 10 to 30 minutes before a bout of cognitive work

00:07:40.380 | or a bout of physical work will increase your focus

00:07:43.060 | by way of increasing acetylcholine and to some extent,

00:07:45.700 | increasing epinephrine as well.

00:07:48.820 | The dopamine increase will have to be achieved

00:07:50.820 | either through cognitive processing,

00:07:53.140 | that is telling yourself you're doing a good job

00:07:54.840 | and moving forward because thoughts really do impact

00:07:57.140 | your levels of dopamine or some other sort of pro-dopamine

00:08:00.740 | or dopamine increasing protocol,

00:08:02.860 | also discussed in the toolkit for focus

00:08:05.120 | and our episode on dopamine for motivation and drive.

00:08:08.020 | So the key thing here to understand

00:08:09.460 | is that the 13 minute a day meditation

00:08:11.540 | is a very effective way to increase focus capacity.

00:08:14.180 | And then in the short term,

00:08:15.440 | if you want to provide a boost now and again to focus,

00:08:18.580 | 300 milligrams of alpha-GPC can be very effective.

00:08:21.360 | There are various sources for that.

00:08:22.700 | Then we'll link to one of them in the show note captions.

00:08:26.020 | By no means am I saying that you need to take alpha-GPC.

00:08:28.740 | A number of people will certainly opt not to.

00:08:30.700 | And a number of people might be saying,

00:08:32.980 | well, I've heard that alpha-GPC can increase focus

00:08:35.340 | by way of increasing acetylcholine and norepinephrine

00:08:38.020 | or epinephrine, but it can also increase TMAO,

00:08:41.060 | which is a kind of a negative marker of cardiac health

00:08:44.140 | and cardiovascular health.

00:08:45.640 | For that reason, I and many others will take 600 milligrams

00:08:48.980 | of a garlic capsule, which can offset that TMAO increase.

00:08:53.340 | It remains uncertain as to how much alpha-GPC

00:08:56.320 | one needs to take before increasing TMAO levels

00:08:59.260 | to a point where it's a concern

00:09:00.620 | that you would even need to take the garlic capsule.

00:09:02.740 | But I just mention it in any case

00:09:04.520 | because it's a pretty simple fix.

00:09:06.300 | Garlic has other health benefits too, of course.

00:09:08.720 | And for most people, 300 milligrams of alpha-GPC

00:09:11.760 | taken every once in a while.

00:09:13.240 | I certainly don't encourage people to take alpha-GPC

00:09:15.780 | every time they want to focus.

00:09:17.640 | I always emphasize behavioral tools first,

00:09:20.580 | then focusing on nutritional tools,

00:09:22.840 | and on occasion using supplement-based tools

00:09:25.460 | to encourage increased levels of focus.

00:09:29.000 | And then of course, there are a number

00:09:31.640 | of different prescription compounds

00:09:33.880 | that if you're working with a board certified physician,

00:09:36.100 | they could prescribe you if you need additional tools

00:09:38.680 | for focus, things like Ritalin, Adderall,

00:09:40.420 | Modafinil, Armodafinil, Vyvanse, et cetera.

00:09:43.120 | For many people are going to be important

00:09:44.880 | and maybe even necessary for people with ADHD, et cetera.

00:09:48.080 | But that's a category into itself.

00:09:49.620 | And as I always say, I'm not a physician,

00:09:51.280 | so I don't prescribe anything.

00:09:52.720 | I'm a professor, so I profess many things.

00:09:55.360 | And today I just wanted to pass along

00:09:57.760 | or redirect your attention to that episode on focus

00:10:01.480 | and highlight those two tools,

00:10:02.800 | the 13-minute-a-day meditation

00:10:04.720 | and 300-milligram Alpha-GPC for increasing focus capacity

00:10:08.680 | and for acutely, that is temporarily,

00:10:11.440 | giving an additional boost for about a focus.

00:10:14.460 | And of course, if you choose not to use those protocols,

00:10:17.080 | that's perfectly fine too.

00:10:18.200 | There's certainly no obligation.

00:10:19.520 | They are simply available to you

00:10:20.760 | should you choose to try them.

00:10:22.920 | And if nothing else, you now have in mind

00:10:25.840 | the neurochemistry of acetylcholine,

00:10:28.080 | epinephrine/adrenaline, and dopamine,

00:10:30.480 | and that will really set the stage for understanding

00:10:32.960 | just how effective and why nicotine is so effective

00:10:37.160 | at increasing focus, motivation,

00:10:39.020 | and even, as you'll soon hear,

00:10:40.700 | working memory and cognitive capacity.

00:10:42.820 | Before we begin, I'd like to emphasize that this podcast

00:10:45.440 | is separate from my teaching and research roles at Stanford.

00:10:48.240 | It is, however, part of my desire and effort

00:10:50.540 | to bring zero cost to consumer information about science

00:10:53.140 | and science-related tools to the general public.

00:10:55.880 | In keeping with that theme,

00:10:56.920 | I'd like to thank the sponsors of today's podcast.

00:10:59.580 | Our first sponsor is Thesus.

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00:11:03.800 | And to be quite direct, I do not like the word nootropics

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00:11:09.560 | And to be direct, again,

00:11:11.840 | there is no such thing as a smart drug.

00:11:13.840 | That is, there's no such thing as a drug

00:11:15.960 | that can make you smarter

00:11:17.440 | because there is no circuit in the brain for being smart.

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00:11:21.300 | there are circuits in the brain for task switching,

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00:14:34.820 | Let's talk about nicotine

00:14:36.140 | and how nicotine impacts our brains, our bodies,

00:14:39.560 | our mental performance, our mental health,

00:14:42.180 | our physical performance, and our physical health.

00:14:45.120 | And once again, I want to remind everybody

00:14:46.700 | that we really need to separate out

00:14:48.580 | a discussion about nicotine

00:14:50.300 | from the discussion about the delivery device for nicotine.

00:14:53.740 | In other words, when we're talking about nicotine,

00:14:56.080 | we are not necessarily talking about smoking,

00:14:58.640 | although we might be.

00:14:59.980 | There are things associated with smoking and with vaping

00:15:03.460 | and other means of getting nicotine into our system

00:15:06.820 | that have their own effects,

00:15:08.600 | both negative and in some cases, positive.

00:15:12.000 | Indeed, later we will talk about

00:15:13.780 | how you can actually use nicotine

00:15:15.600 | to get over smoking addiction.

00:15:17.100 | This won't come as a surprise to many people,

00:15:19.180 | but what perhaps will come as a surprise

00:15:21.380 | is the fact that many people

00:15:22.420 | actually use nicotine-like substances or nicotine itself

00:15:26.040 | in order to relieve nicotine addiction.

00:15:28.500 | So we'll talk about that and what that looks like

00:15:30.420 | and offer various protocols for you later in the episode.

00:15:34.220 | I also want to mention here at the outset

00:15:35.700 | that I have a longstanding interest in nicotine.

00:15:38.620 | In fact, early in my scientific career,

00:15:40.680 | I did research on nicotine and its role in brain development

00:15:44.500 | and I've had a longstanding interest in neuroplasticity,

00:15:47.880 | the brain's ability to change in response to experience.

00:15:50.500 | And so experiments that have been done

00:15:51.840 | by close colleagues and friends of mine

00:15:53.500 | have really emphasized the fact that acetylcholine

00:15:56.100 | and in particular, when acetylcholine

00:15:58.480 | activates so-called nicotinic receptors,

00:16:01.340 | something you'll learn more about in a little bit,

00:16:03.640 | that can actually serve as a gateway or a trigger

00:16:06.900 | for directed rewiring of the brain.

00:16:09.180 | So this is fascinating.

00:16:10.100 | We think of nicotine as something that we take,

00:16:12.380 | but actually we have receptors,

00:16:14.660 | that is locations in the brain to which nicotine binds

00:16:18.660 | and can exert its effects.

00:16:20.680 | And those receptors did not come about

00:16:22.280 | because of the existence of tobacco

00:16:24.140 | or the existence of vaping pens

00:16:25.940 | or because of the existence of anything in the outside world.

00:16:28.980 | The fact that there are nicotinic receptors

00:16:32.560 | in our brain and body

00:16:34.520 | tells you that acetylcholine and nicotine themselves

00:16:37.840 | have very important roles in normal brain and body function.

00:16:41.640 | So much so that I often like to point to an anecdote

00:16:44.540 | of a very well-known Nobel prize winning neuroscientist.

00:16:48.300 | I won't reveal who they are.

00:16:49.460 | They're not a faculty member at Stanford,

00:16:50.960 | but many neuroscientists know of this person

00:16:54.300 | and many people in the outside world know of this person.

00:16:56.460 | And they are also well-known for their love of nicotine.

00:17:00.960 | I once sat in this person's office and he,

00:17:03.420 | I will reveal it as a he,

00:17:04.720 | consumed no fewer than three pieces of nicotine gum

00:17:10.340 | during that relatively short conversation

00:17:12.380 | of about 45 minutes.

00:17:13.860 | And that was surprising to me.

00:17:15.500 | And I asked him why he was taking so much nicotine

00:17:19.280 | through nicotine gum.

00:17:20.540 | And he replied that for years he had been a chronic smoker,

00:17:23.700 | which on the one hand had greatly impaired

00:17:26.160 | his cardiovascular health and his fitness,

00:17:28.020 | no surprise there.

00:17:28.860 | And we'll talk a little bit more about

00:17:29.980 | what the underlying reasons are.

00:17:31.620 | But most everyone, if not everyone knows

00:17:33.900 | that smoking cigarettes or smoking in general

00:17:37.260 | really impairs lung health.

00:17:38.840 | There's just simply no question about it.

00:17:40.680 | There are some more or less unhealthy ways to smoke,

00:17:44.880 | but the quite honest message is that smoking of any kind

00:17:48.480 | is going to disrupt lung endothelial function,

00:17:51.240 | lung function, blood vessels, and so forth.

00:17:53.640 | It's going to make it harder to breathe with vigor,

00:17:55.520 | take deep breaths, deliver oxygen to tissues, et cetera.

00:17:58.840 | That said, he also pointed out

00:18:01.280 | that the data on nicotine specifically

00:18:04.660 | are pointing to the fact that nicotine can be,

00:18:08.240 | can be protective against certain forms

00:18:11.000 | of cognitive impairment.

00:18:12.600 | And that is why he continued to chew

00:18:14.800 | nicotine containing gum.

00:18:16.320 | And he swore by the focus enhancing

00:18:18.520 | and motivation enhancing effects of nicotine containing gum.

00:18:22.240 | Now that is not a call to arms for you to run out

00:18:24.720 | and start chewing or consuming nicotine containing products.

00:18:28.520 | We will talk about those products later in the episode,

00:18:30.760 | some of their potential advantages,

00:18:32.240 | some of their potential disadvantages.

00:18:34.120 | Now I share this anecdote because it nicely separates

00:18:37.380 | nicotine from the delivery device

00:18:39.220 | through which nicotine arrives.

00:18:41.320 | Now I haven't talked to this individual in a few years

00:18:43.960 | to see whether or not the nicotine is working

00:18:46.720 | to stave off any kind of Alzheimer's or neurodegenerative

00:18:49.600 | or cognitive impairment that would come with age.

00:18:52.200 | This gentleman is getting up in the years

00:18:55.040 | and seems quite sharp nonetheless,

00:18:57.200 | but then again was always exceedingly sharp.

00:19:00.160 | The point is nicotine is a substance

00:19:03.720 | that can both promote cognitive function

00:19:06.640 | and under some conditions if taken to inappropriate

00:19:10.820 | or I should say to extreme dosages

00:19:12.680 | can also impair cognitive function.

00:19:14.740 | So today we really need to have a nuanced conversation

00:19:17.200 | about nicotine.

00:19:18.200 | One that includes some of the benefits,

00:19:20.020 | some of the drawbacks in particular for children,

00:19:23.380 | certainly for people that are pregnant,

00:19:25.680 | for people that have addictive tendencies

00:19:27.840 | and for people that have depression

00:19:29.780 | and any other kind of mood disorders.

00:19:32.340 | What I will tell you soon is that nicotine

00:19:35.480 | can be very powerful as a mood modulator.

00:19:38.620 | And many people who have tried to quit nicotine

00:19:41.440 | mainly through the form of smoking

00:19:43.440 | will find that their mood can drop substantially.

00:19:46.360 | So nicotine does a lot of things in the brain and body.

00:19:49.120 | And so I'd like to begin by talking about

00:19:50.960 | what exactly nicotine is

00:19:52.960 | and how it impacts your brain and body.

00:19:55.340 | So what is nicotine and where is it found?

00:19:57.540 | Obviously nicotine is found in the tobacco plant,

00:20:00.400 | but nicotine is also found in nightshades.

00:20:03.680 | That is tomatoes, eggplants and sweet peppers.

00:20:07.200 | Although the concentrations of nicotine

00:20:09.240 | in tomatoes, eggplants and sweet peppers

00:20:11.100 | is vastly lower than it is in the tobacco plant.

00:20:15.040 | You actually can also find nicotine in potatoes.

00:20:18.120 | Now, why is nicotine present in potatoes and tomatoes

00:20:21.800 | and in the tobacco plant at all?

00:20:24.120 | Well, nicotine is a plant alkaloid.

00:20:26.440 | We'll get into alkaloids a little bit later,

00:20:28.340 | but it is thought that these alkaloids evolved in plants

00:20:31.920 | as a way to prevent insects from eating them.

00:20:35.960 | And without going into a lot of insect biology,

00:20:38.200 | the reason or the rationale behind this explanation

00:20:40.920 | is that nicotine is not only a substance in tobacco

00:20:44.400 | that people use or in the various medications

00:20:46.320 | that people use, but it's also used as a pesticide

00:20:49.240 | because it can dramatically disrupt

00:20:51.640 | the nervous system of insects.

00:20:54.000 | It can render them infertile,

00:20:55.760 | which is not to say that it renders humans infertile.

00:20:58.320 | I want to say again, it is not the case

00:21:00.340 | that nicotine renders humans infertile,

00:21:02.320 | but it can make certain insects infertile.

00:21:04.640 | It can actually disrupt their motor function

00:21:06.760 | and their brain function.

00:21:07.960 | And the reasons that it has such different effects

00:21:10.440 | on insects, in other words,

00:21:11.920 | it can kill them or prevent them from reproducing

00:21:14.920 | and therefore explains why plants probably evolved

00:21:18.520 | to have this plant alkaloid, nicotine.

00:21:20.620 | In humans, because of the differences

00:21:23.160 | in receptors for nicotine,

00:21:25.960 | where they're located in the types of receptors,

00:21:28.380 | the effects of nicotine on humans is quite a bit different.

00:21:31.320 | And again, it does not cause infertility in humans.

00:21:33.960 | Although I will talk a little bit later

00:21:35.680 | about some double-blind peer-reviewed studies

00:21:37.380 | conducted in humans that indicate that for instance,

00:21:41.600 | nicotine can reduce penile girth,

00:21:44.240 | that is the girth of the penis,

00:21:45.440 | and can lead to certain forms of sexual dysfunction.

00:21:48.680 | And those changes are largely downstream of changes

00:21:51.880 | in blood flow and endothelial cell function.

00:21:55.000 | Endothelial cells are the cells that make up blood vessels

00:21:57.720 | and other vascular type tissues within the brain and body.

00:22:00.940 | So nicotine is found in these plants.

00:22:02.960 | And what we can know for sure is that at some point

00:22:06.260 | in human evolution, somebody or some group of people,

00:22:09.940 | either, and here I'm completely guessing,

00:22:12.320 | it's a just so story,

00:22:14.440 | but someone or some group must have inhaled the smoke

00:22:18.920 | from the tobacco plant or put the dried leaves

00:22:22.680 | of the tobacco plant against some mucosal tissue,

00:22:26.000 | any of the different mucosal linings of their body

00:22:27.880 | by which substances can pass through, that's right.

00:22:31.120 | Any of the mucosal soft lining tissues of the body

00:22:34.440 | will allow certain substances,

00:22:36.160 | not all certain substances to pass in.

00:22:37.940 | That's why people can put tobacco in their mouth

00:22:39.760 | and a certain amount of nicotine

00:22:40.720 | makes it into the bloodstream, put tobacco up their nose,

00:22:43.640 | certain amount of nicotine gets into the bloodstream.

00:22:45.360 | I haven't heard of people putting tobacco

00:22:47.200 | in other orifices of their body containing mucosal tissue.

00:22:49.680 | And I'm certainly not suggesting people do that,

00:22:51.720 | but you get the idea and how nicotine gets from these plants,

00:22:54.820 | these dried leaves into the bloodstream.

00:22:57.500 | Burning tobacco leads to a heat-induced change

00:23:02.280 | in the availability of nicotine.

00:23:04.000 | And this is why smoking tobacco or vaping tobacco

00:23:08.720 | simply by heating it up allows the nicotine to be liberated

00:23:12.200 | and go into the bloodstream

00:23:13.780 | simply by inhaling it into the lungs.

00:23:15.320 | We will get back to smoking of various kinds later,

00:23:18.100 | but right now let's just keep our attention

00:23:20.600 | on how nicotine is pulled from these plants

00:23:24.200 | and into the human body.

00:23:25.880 | Now, whether by inhalation or whether or not

00:23:28.480 | by placing it in contact with the mucosal tissue of the mouth

00:23:31.720 | or other mucosal containing orifice of the body,

00:23:36.000 | the nicotine then gets into the bloodstream.

00:23:38.360 | And once it's in the bloodstream,

00:23:40.280 | it only exerts its effects

00:23:41.960 | because it binds to certain so-called nicotinic receptors.

00:23:46.480 | Okay, so the nicotinic receptors

00:23:49.040 | are of the acetylcholinergic variety.

00:23:51.800 | I know this is a lot to think about and a lot to hear

00:23:53.920 | if you haven't heard about this,

00:23:54.760 | but it's actually quite simple.

00:23:56.060 | Anyone can understand this.

00:23:57.700 | Acetylcholin is a molecule, a chemical that is,

00:24:02.280 | that's released in the brain and body.

00:24:05.720 | And when it binds to receptors,

00:24:07.640 | that is little parking spots on cells,

00:24:09.640 | it changes the way those cells behave.

00:24:11.880 | Those cells can increase their activity

00:24:13.840 | and release other chemicals.

00:24:14.920 | They can become electrically active.

00:24:16.220 | They can do any number of different things.

00:24:19.100 | When we ingest nicotine, it gets into the bloodstream

00:24:22.760 | and eventually some of that will get into the brain

00:24:24.620 | and some of it gets into the body.

00:24:26.080 | And in both of the brain and body,

00:24:27.620 | there are these so-called nicotinic acetylcholine receptors.

00:24:30.700 | Now the so-called family, and indeed they are a family,

00:24:34.280 | this is how we refer to groups of receptors

00:24:36.840 | of related design and genetic background, just like humans.

00:24:40.760 | You have a family of these acetylcholine receptors

00:24:43.600 | that are of the nicotinic variety.

00:24:44.900 | So, you know, maybe on one street in your neighborhood,

00:24:46.880 | you know the Joneses on another street,

00:24:48.440 | you know the Chows on another street.

00:24:49.740 | Well, in your body,

00:24:50.960 | you have the nicotinic acetylcholine receptors

00:24:53.120 | and then you have the so-called

00:24:53.960 | muscarinic acetylcholine receptors.

00:24:56.120 | Today, it's really simple.

00:24:57.160 | Nicotine only binds to the nicotinic acetylcholine receptors

00:25:00.000 | and there are a bunch of different ones

00:25:01.620 | on a bunch of different tissues.

00:25:03.160 | And the differences in those receptors

00:25:05.940 | dictate what sorts of effects

00:25:08.660 | the nicotine will have on those tissues.

00:25:11.360 | So let's talk about what those effects are

00:25:13.000 | and let's do that by dividing the effects of nicotine

00:25:15.480 | into effects on the brain.

00:25:17.080 | So everything from the neck up and on the body,

00:25:19.620 | the so-called central nervous system and the periphery.

00:25:22.080 | Although I want to point out that your spinal cord

00:25:23.520 | is part of the central nervous system,

00:25:24.740 | so in fairness to the reality,

00:25:27.340 | your brain and spinal cord are all central nervous system,

00:25:30.360 | everything else is considered the periphery.

00:25:32.880 | Now, there are a lot of different

00:25:33.900 | nicotinic acetylcholine receptors,

00:25:35.700 | but for those of you that want to know,

00:25:37.260 | you have aficionados or if you're ultra curious about this,

00:25:40.740 | the main effects of nicotine in the brain

00:25:43.520 | are mediated by nicotine binding

00:25:46.260 | to the so-called alpha-4 beta-2 receptor,

00:25:49.760 | alpha-4 beta-2 receptor.

00:25:52.100 | Even if you don't care about receptor subtypes,

00:25:54.520 | that's going to come up later

00:25:55.640 | when we discuss why nicotine suppresses appetite.

00:25:59.320 | In fact, one of the major reasons

00:26:00.640 | why people don't want to quit smoking

00:26:02.960 | or they quit smoking or another form of ingesting nicotine

00:26:06.520 | and then they relapse, they go back to smoking

00:26:10.100 | or ingesting nicotine in some other way

00:26:12.000 | is because indeed nicotine will increase metabolism

00:26:15.800 | and reduce hunger in large part

00:26:18.200 | by binding to this alpha-4 beta-2 receptor

00:26:20.840 | in a particular area of the brain.

00:26:21.920 | We're going to return to that in a little bit,

00:26:23.060 | but if you've ever heard that nicotine kills the appetite,

00:26:26.040 | indeed it does.

00:26:27.440 | It's not the behavior of smoking itself,

00:26:29.080 | it's not because you always have a cigarette in your mouth

00:26:30.700 | that you're not eating more food,

00:26:32.040 | although I suppose that might be a minor effect.

00:26:34.220 | There are direct effects of nicotine on both appetite,

00:26:37.480 | that is it reduces appetite,

00:26:38.920 | and direct effects on metabolism,

00:26:40.700 | that is it increases metabolism

00:26:42.320 | through its effects on some other areas of the brain and body

00:26:44.560 | we'll talk about in a moment.

00:26:45.880 | And within the brain,

00:26:47.200 | nicotine binds to this alpha-4 beta-2 receptor

00:26:51.200 | in various locations in the brain.

00:26:52.880 | And there are three and maybe a fourth

00:26:55.200 | that we'll talk about neurochemical effects of nicotine

00:26:58.400 | after you ingest it.

00:26:59.520 | First things first, when you ingest nicotine

00:27:01.920 | by smoking nicotine containing tobacco,

00:27:05.340 | or if you place tobacco in contact with the mucosal lining

00:27:09.840 | of the nasal passages of the mouth,

00:27:12.160 | takes about two to 15 minutes

00:27:15.360 | for that nicotine to enter the bloodstream.

00:27:16.840 | Smoking hits the bloodstream faster,

00:27:18.840 | vaping even faster, I should mention,

00:27:21.360 | for a variety of reasons,

00:27:22.800 | and placing tobacco directly in contact

00:27:26.120 | with the mucosal lining is going to be the slowest.

00:27:28.760 | Now, as I mentioned before,

00:27:29.960 | nicotine gets into the bloodstream,

00:27:31.400 | and then because nicotine can pass

00:27:33.400 | through the so-called blood-brain barrier, the BBB,

00:27:36.640 | which is basically a fence around the brain,

00:27:39.040 | because it can pass through the blood-brain barrier,

00:27:41.320 | it's going to have very rapid effects on the brain

00:27:43.520 | in these four major categories

00:27:45.600 | of neurochemicals and neural circuits.

00:27:48.840 | The first of those categories,

00:27:50.400 | and this is a very important one,

00:27:52.080 | this is one that was brought up in the episode

00:27:53.640 | on dopamine motivation and drive,

00:27:55.080 | and I think not just all scientists,

00:27:57.200 | but all human beings should know that within their brain,

00:28:00.200 | they have what is called the mesolimbic reward pathway.

00:28:05.200 | The mesolimbic reward pathway,

00:28:06.600 | if you just want to call it the dopamine reward pathway,

00:28:09.320 | is, as the name suggests,

00:28:11.040 | a set of connections between a brain area

00:28:12.940 | called the ventral tegmental area.

00:28:14.480 | You don't have to remember the names of these things,

00:28:16.460 | of course, but if you want to, that's fine too.

00:28:18.740 | The ventral tegmental area, or VTA,

00:28:21.160 | connects to another area called the nucleus accumbens.

00:28:24.880 | Now, here's what's very important.

00:28:26.400 | Nicotine triggers the release of dopamine

00:28:30.400 | from the nucleus accumbens.

00:28:31.640 | This is what gives nicotine its rewarding properties.

00:28:34.720 | It increases motivation.

00:28:36.100 | It tends to give a not so subtle,

00:28:39.220 | but very transient increase in feelings of wellbeing

00:28:42.860 | and alertness and motivation,

00:28:44.740 | and that's because of the increase in dopamine

00:28:46.760 | caused by nicotine directly within the nucleus accumbens.

00:28:50.560 | Nicotine also triggers the release of certain neurochemicals

00:28:55.260 | from the ventral tegmental area itself,

00:28:57.500 | and those impinge on nucleus accumbens

00:28:59.820 | and increase dopamine levels further.

00:29:02.180 | This is what makes the rewarding properties,

00:29:04.560 | or sometimes referred to as the reinforcing properties

00:29:07.180 | of nicotine, so powerful.

00:29:08.700 | This is why so many billions of people ingest nicotine

00:29:13.080 | in one form or another.

00:29:14.100 | It's also why nicotine is so hard to quit,

00:29:18.100 | because there's a potent increase in dopamine

00:29:20.820 | from multiple neural circuit pathways

00:29:23.080 | within this mesolimbic reward circuitry.

00:29:26.300 | Now, within the mesolimbic reward circuitry,

00:29:29.020 | there's an interesting feature.

00:29:29.940 | There are accelerators that essentially

00:29:32.020 | push out more dopamine, get more dopamine released,

00:29:34.860 | and there are breaks of the so-called GABAergic variety.

00:29:37.780 | GABA is an inhibitory neurotransmitter.

00:29:39.920 | You don't need to know too much about it

00:29:41.040 | to just understand that nicotine both increases dopamine,

00:29:45.620 | but also decreases the activity of GABA.

00:29:49.340 | And so this is like pushing on the accelerator for dopamine,

00:29:52.720 | but also removing the break.

00:29:54.660 | So there's a two-pronged effect of nicotine

00:29:57.900 | on reinforcement reward dopamine-related pathways,

00:30:01.260 | the feel-good motivation pathways,

00:30:03.940 | and that is an increase in dopamine

00:30:06.400 | and a decrease in GABA.

00:30:08.500 | And again, that's all mediated

00:30:09.860 | through this mesolimbic reward pathway

00:30:11.340 | involving the ventral tegmental area

00:30:13.260 | and the nucleus accumbens.

00:30:14.660 | So if you can conceptualize even just 5%

00:30:17.120 | of what I just told you,

00:30:18.260 | or even if you can just remember,

00:30:19.540 | nicotine increases dopamine,

00:30:21.260 | and that's why it feels so good,

00:30:22.620 | it makes you want more of it,

00:30:24.660 | you will have everything you need to know in mind

00:30:27.340 | in order to understand both why nicotine is so highly used

00:30:32.340 | and indeed abused, why it's so hard to quit,

00:30:35.200 | and that will point to avenues

00:30:36.740 | as to how to quit or reduce intake.

00:30:39.080 | And it also points to how nicotine can actually be used

00:30:42.160 | in an antidepressant way should you choose,

00:30:45.660 | and we will talk about what the various criteria are

00:30:48.180 | for choosing that.

00:30:49.340 | But just understand nicotine increases motivation,

00:30:53.020 | it decreases negative feelings of mood,

00:30:55.660 | it increases positive feelings of mood and motivation.

00:30:58.420 | Before we continue with today's discussion,

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00:32:11.760 | The second major effect that nicotine has in the brain

00:32:14.440 | is that it increases acetylcholine.

00:32:17.080 | Acetylcholine is a neuromodulator that exists in you and me.

00:32:20.520 | It is released from multiple sites in the brain.

00:32:23.520 | And the two major sites are the nucleus basalis.

00:32:27.400 | So these are a collection of neurons

00:32:29.760 | in the front and base of your brain

00:32:32.140 | and from some brain stem areas.

00:32:34.000 | And there are a bunch of different ones back there

00:32:35.980 | in your brain stem, which is indeed in the back,

00:32:37.880 | that release acetylcholine.

00:32:39.760 | That include the locus coeruleus as kind of a minor site,

00:32:42.400 | the pedunculopontine nucleus.

00:32:44.300 | There are a bunch of these different areas,

00:32:46.720 | the parabigeminal nucleus.

00:32:48.200 | There are a bunch of these things back there.

00:32:49.800 | We don't have to go into all the names,

00:32:51.280 | but just understand that there are little pockets of neurons,

00:32:53.700 | nerve cells located in the front and the back

00:32:55.920 | and some extent in the middle of your brain,

00:32:57.480 | but really in the front and the back of your brain

00:32:59.400 | that can serve two major roles.

00:33:02.280 | Here they are.

00:33:03.960 | Acetylcholine released from nucleus basalis

00:33:06.520 | leads to a sort of spotlighting or highlighting

00:33:09.560 | a particular neural circuits in the brain.

00:33:11.780 | What do I mean by this?

00:33:12.620 | Well, let's say you're working on a puzzle.

00:33:14.800 | Let's say it's a cognitive puzzle.

00:33:15.920 | Maybe you're doing a word puzzle.

00:33:17.520 | Or nowadays I've heard of this wordle thing.

00:33:19.520 | I'm on Twitter and people are always posting

00:33:21.000 | their wordle thing.

00:33:21.880 | I have no idea what it is,

00:33:22.880 | but I'm guessing it's some sort of puzzle.

00:33:24.580 | I'm guessing it's like a crossword puzzle.

00:33:26.040 | And here, if I'm wrong, I don't know, educate me.

00:33:27.800 | Tell me what wordle is.

00:33:28.640 | Somebody put it in the comments

00:33:29.960 | and tell me if I should play it or not.

00:33:32.180 | Here's the deal.

00:33:33.020 | When acetylcholine is released from nucleus basalis,

00:33:36.840 | the neurons are there in the base of the brain,

00:33:39.440 | but they extend axons,

00:33:41.000 | which are like little wires elsewhere in the brain.

00:33:43.080 | And when acetylcholine is released,

00:33:45.000 | it tends to be released at particular locations in the brain

00:33:47.680 | that are associated with whatever activity

00:33:49.600 | we happen to be doing.

00:33:50.500 | So if I'm doing wordle,

00:33:52.340 | here I'm talking about it as if I've ever done it,

00:33:54.200 | doing a crossword puzzle or wordle,

00:33:56.000 | well, the neurons that were involved

00:33:57.240 | in trying to figure out the solution

00:33:58.560 | to that wordle or crossword puzzle are active.

00:34:00.900 | And then acetylcholine is released from the little wires,

00:34:03.640 | the little endings of these cells in nucleus basalis.

00:34:06.560 | And all of a sudden, those neural circuits get a boost.

00:34:09.460 | They become more active.

00:34:10.920 | And believe it or not,

00:34:12.680 | our ability to perform that crossword puzzle,

00:34:14.640 | or at least focus on that wordle or crossword puzzle

00:34:17.800 | gets enhanced.

00:34:19.040 | It literally increases.

00:34:20.400 | Our attention for that and not anything else is enhanced.

00:34:23.760 | So it's literally like a neurochemical attentional spotlight.

00:34:27.840 | Nicotine increases acetylcholine

00:34:30.200 | and thereby focusing concentration and mental performance,

00:34:33.440 | not by changing the neural circuits

00:34:36.020 | that are activated per se,

00:34:37.760 | but rather by making more acetylcholine available

00:34:42.100 | at those release sites.

00:34:43.560 | So it's as if the spotlighter got more intense.

00:34:46.320 | The highlighter is more intense than it would be otherwise.

00:34:49.360 | And I should also mention

00:34:50.840 | because of the so-called pharmacokinetics,

00:34:52.800 | the time course in which nicotine has its effects,

00:34:55.920 | which are pretty short-lived.

00:34:57.400 | Talk about those in a moment.

00:34:58.720 | This enhancement in cognitive performance and attention

00:35:02.320 | is going to be very transient,

00:35:03.400 | probably on the order of about 30, maybe 45 minutes.

00:35:06.840 | The half-life of nicotine,

00:35:07.980 | depending on how it's ingested

00:35:09.200 | and whether or not you have food in the gut

00:35:10.380 | and what else is in the bloodstream, et cetera,

00:35:12.080 | it's going to be anywhere from one to two hours.

00:35:14.480 | But typically the effects of nicotine

00:35:15.880 | will come on in about two to 15 minutes,

00:35:18.000 | as I mentioned before,

00:35:18.960 | and then will last anywhere from about 30 to 45 minutes.

00:35:22.440 | This is why in the old days,

00:35:24.000 | and still to some extent in certain areas of the world,

00:35:26.420 | but less so in the United States

00:35:28.240 | and certainly in Europe as well,

00:35:30.080 | we don't see quite as many people smoking cigarettes

00:35:32.640 | for reasons we can discuss later.

00:35:34.860 | But you would see these chain smokers

00:35:37.120 | who are trying to maintain constant levels of nicotine

00:35:40.440 | in their brain and bloodstream.

00:35:41.960 | Now, perhaps they didn't know

00:35:43.580 | that nicotine has this one to two hour half-life,

00:35:46.320 | but they could sense, no doubt,

00:35:48.700 | the cognitive and the physical effects of nicotine,

00:35:50.960 | including this cognitive enhancement effect

00:35:52.840 | and highlighting of the neural circuits effect.

00:35:55.240 | And they would notice they would smoke a cigarette

00:35:57.600 | and then for the next five to 45 minutes

00:36:00.160 | have heightened focus and then it would start to drop off.

00:36:02.120 | So they smoke another cigarette.

00:36:03.140 | So in other words,

00:36:03.980 | they're trying to maintain a constant level of nicotine

00:36:07.320 | for whatever activities they needed to perform.

00:36:09.320 | Obviously chain smoking

00:36:10.760 | because of the terrible effects of smoking.

00:36:13.560 | I'll talk about those terrible effects,

00:36:14.780 | but I'm sure you've heard of them before.

00:36:16.680 | Cancer, depletion of just about every organ and body tissue

00:36:20.640 | to the point that it can actually be measured

00:36:22.780 | how many years of your life you're peeling off

00:36:24.680 | in terms of lifespan and health span by smoking.

00:36:27.340 | Well, the terrible effects of smoking are indisputable,

00:36:31.360 | but the positive effects of nicotine on this circuitry

00:36:35.160 | are part of the reason why people would chain smoke

00:36:37.780 | in the first place,

00:36:38.960 | rather than get one big peak of concentration and focus

00:36:41.700 | and then just let it disappear after 45 minutes.

00:36:44.520 | Okay, so what we have is a scenario

00:36:46.840 | where dopamine is going up in the mesolimbic pathway.

00:36:49.540 | That's why smoking or ingesting nicotine in any other way

00:36:52.380 | feels good and makes us feel motivated.

00:36:54.660 | And then the increase in acetylcholine,

00:36:56.220 | especially from nucleus basalis in the front of the brain

00:36:58.580 | is the reason why it can increase our ability

00:37:01.360 | to focus on particular types of endeavors,

00:37:04.220 | particular mental work that we're doing,

00:37:05.820 | or maybe even particular physical work.

00:37:07.640 | Although I should mention anytime I'm pairing

00:37:09.780 | the words nicotine and physical work,

00:37:11.800 | it's obvious that because of the ways

00:37:13.700 | that smoking impairs lung function,

00:37:16.200 | those two things really run counter to one another.

00:37:18.540 | In other words, if you are thinking about ingesting nicotine

00:37:21.340 | through smoking or vaping

00:37:22.380 | in order to improve physical performance,

00:37:25.140 | that's a terrible idea.

00:37:26.400 | The logic isn't there

00:37:27.400 | and the health detriments are certainly there.

00:37:29.220 | The third neurochemical pathway that's strongly activated

00:37:32.640 | when nicotine is brought into the central nervous system,

00:37:35.060 | into the brain is epinephrine or in particular norepinephrine

00:37:39.300 | which is related to epinephrine.

00:37:40.600 | Now, earlier I said epinephrine is the same as adrenaline.

00:37:43.180 | That's still true.

00:37:44.280 | Norepinephrine is closely related to epinephrine.

00:37:46.280 | And for today's discussion,

00:37:47.420 | we're going to use them interchangeably.

00:37:48.860 | Although I realize as I say that,

00:37:51.160 | that the medical students and some biology students

00:37:53.100 | are probably going to have a minor seizure

00:37:54.860 | when I lump norepinephrine and epinephrine.

00:37:57.060 | I don't do that to be too much of a lumper.

00:37:59.980 | In science, we talk about lumpers and splitters.

00:38:01.820 | Lumpers are people that like to oversimplify a little bit.

00:38:04.040 | Splitters are people that really like to detail.

00:38:05.940 | You'll see a lot of splitters on social media

00:38:07.860 | from time to time.

00:38:08.700 | They'll say, "Wait, you didn't mention

00:38:10.300 | the alpha-2 beta-6 receptor subunit."

00:38:13.060 | Okay, look, I get it.

00:38:14.580 | And I am all for having splitters in the room.

00:38:17.100 | But for sake of today's discussion

00:38:18.900 | and for ease of digestibility of some of this,

00:38:21.980 | just want to point out that norepinephrine, epinephrine,

00:38:24.100 | and adrenaline, I'm going to treat as a common pool

00:38:26.340 | of similar, in fact, very similar molecules

00:38:29.100 | that all have the same net effect,

00:38:31.700 | at least in the context of this discussion.

00:38:33.200 | And that's to increase levels of alertness,

00:38:35.340 | energy, and arousal.

00:38:37.020 | And the way that nicotine accomplishes those increases

00:38:39.580 | in alertness and arousal and energy within the brain

00:38:42.860 | is by triggering the release of norepinephrine

00:38:44.620 | from a little cluster of neurons in the back of the brain

00:38:46.380 | called locus coeruleus, tiny cluster of neurons

00:38:49.900 | that offers up, or I should say has,

00:38:52.580 | because they're always there from birth,

00:38:54.980 | has these little wires, these axons that extend many,

00:38:58.040 | many places in the brain, not every place,

00:38:59.780 | but virtually every place and can sprinkler the brain

00:39:02.620 | with norepinephrine and essentially serve

00:39:03.980 | as a wake-up signal, elevating levels of energy.

00:39:07.260 | And when that combines with the acetylcholine

00:39:10.020 | from nucleus basalis,

00:39:12.140 | which causes attentional spotlighting,

00:39:14.020 | increases in concentration and focus,

00:39:16.500 | and with the feel-good properties of dopamine

00:39:19.300 | and the motivating properties of dopamine released

00:39:21.620 | from the mesolimbic reward pathway,

00:39:23.700 | now you can start to get a picture

00:39:25.580 | of why nicotine is such a powerful molecule.

00:39:30.140 | It's making people feel motivated and good.

00:39:32.020 | It's making people feel focused

00:39:33.540 | and it makes people feel alert

00:39:36.300 | when they would otherwise feel a little bit sleepy.

00:39:38.460 | So this is a really powerful compound.

00:39:40.420 | In fact, going back to our earlier discussion about focus

00:39:43.940 | and some tools for focus, and I encourage you,

00:39:45.800 | if you're interested to please check out the episode

00:39:47.540 | on focus, there are a number of different tools

00:39:49.740 | and protocols there to increase focus,

00:39:51.660 | but here we're talking about one molecule,

00:39:55.460 | nicotine found in plants like tomatoes and potatoes

00:39:59.180 | and the tobacco plant, and it can be synthesized

00:40:02.420 | in a laboratory and ingested through a patch or a gum

00:40:05.780 | or even a pill or a toothpick dipped in nicotine.

00:40:09.440 | One molecule that can trigger activation

00:40:12.980 | of all the circuits for focus and motivation

00:40:16.540 | in one fell swoop.

00:40:19.100 | That is remarkable.

00:40:20.660 | That is absolutely remarkable.

00:40:22.140 | And here we haven't even touched

00:40:23.060 | on some of the psychological components of focus, right?

00:40:25.160 | Whether or not we're interested in something,

00:40:26.600 | whether or not we're excited about it or not.

00:40:28.860 | This is a very, very powerful system.

00:40:31.340 | So powerful, in fact, that I think we can really place

00:40:34.260 | nicotine right up there at the top, right next to caffeine

00:40:38.620 | as the molecule that has fundamentally changed

00:40:42.780 | human evolution, human consciousness, and human experience.

00:40:46.760 | Even if you're somebody who's never ingested nicotine,

00:40:49.340 | this absolutely has to be true

00:40:50.780 | because you have these nicotinic receptors,

00:40:52.700 | which is to say that acetylcholine that's naturally released

00:40:55.540 | without any external trigger within your brain and body,

00:40:58.900 | or I should say without any trigger from nicotine

00:41:01.140 | in particular, is binding these

00:41:03.420 | nicotinic acetylcholine receptors

00:41:05.420 | and is creating these effects in your brain and body.

00:41:07.700 | It's just absolutely staggering.

00:41:09.460 | Now, earlier I mentioned the appetite suppressing

00:41:12.180 | and indeed metabolism increasing effects of nicotine.

00:41:15.540 | And while that's a fairly niche component

00:41:18.180 | of what nicotine does, I mean, it's an important one,

00:41:20.540 | but it's not the major reason

00:41:22.260 | why most people consume nicotine.

00:41:24.260 | I'd like to take a moment and talk about that now

00:41:25.920 | because we are in the brain and we're talking

00:41:27.900 | about the effects of nicotine in the brain.

00:41:29.500 | And so it seems to me the appropriate time

00:41:31.220 | to talk about this.

00:41:32.120 | Now we can have this conversation about nicotine

00:41:34.500 | and appetite and metabolism in a very simple

00:41:36.540 | and straightforward way.

00:41:38.020 | If you'd like to learn more about the biology

00:41:40.900 | of metabolism and appetite

00:41:43.180 | and how those things are mediated by neural components.

00:41:46.180 | So not just stuff like your liver, et cetera,

00:41:48.180 | we have episodes on that,

00:41:49.220 | but really the neural components of hunger and appetite.

00:41:52.140 | I encourage you to check out our episode

00:41:53.500 | on hunger and appetite.

00:41:55.260 | But in that episode, we had a discussion

00:41:58.180 | and it's one that I'll just briefly summarize now

00:42:00.760 | that you have a collection of neurons

00:42:02.300 | that sits right above the roof of your mouth or so

00:42:04.660 | called the hypothalamus.

00:42:06.060 | Hypo means below and thalamus is right above it,

00:42:08.540 | hypothalamus.

00:42:09.500 | So the small collection of neurons in the hypothalamus

00:42:12.660 | do a number of different things related to sex behavior,

00:42:15.520 | aggression, mediating the temperature of your body, et cetera,

00:42:19.060 | but also appetite and suppressing appetite.

00:42:22.100 | And within the hypothalamus,

00:42:23.220 | there's a compact collection of these little neurons,

00:42:26.120 | which are referred to as the POMC, P-O-M-C neurons.

00:42:28.980 | And the name comes from the fact

00:42:29.940 | that they express certain peptides

00:42:31.220 | and we won't get into that now,

00:42:32.720 | but the POMC neurons have a very profound impact

00:42:37.020 | on whether or not you feel hungry

00:42:38.620 | or whether or not you do not feel hungry,

00:42:40.980 | whether or not your appetite is suppressed.

00:42:43.380 | It turns out that when nicotine gets into the bloodstream

00:42:45.540 | and then into the brain,

00:42:46.840 | some of that nicotine binds to nicotinic alpha-4 beta-2

00:42:51.740 | containing nicotinic receptors.

00:42:53.820 | Again, these subunits are receptors,

00:42:55.180 | but basically the nicotine binds

00:42:56.340 | to one of those parking spots, parks there.

00:42:58.020 | And as a consequence, these POMC, P-O-M-C neurons

00:43:00.900 | increase their electrical activity

00:43:03.400 | and appetite is suppressed.

00:43:05.680 | And that's because the POMC neurons have outputs

00:43:08.540 | to various areas of the brain and body

00:43:10.560 | controlling everything from how full we feel

00:43:13.940 | to whether or not our blood sugar goes up or down,

00:43:17.340 | which can impact our hunger.

00:43:18.980 | And believe it or not, whether or not we have a tendency

00:43:21.320 | to want to move the jaw of our mouth in order to chew food.

00:43:24.700 | Yes, believe it or not, the neural circuitry associated

00:43:27.180 | with appetite and suppression of appetite

00:43:29.620 | actually dictates whether or not you prefer to,

00:43:32.660 | or I should say are more biased or less biased

00:43:35.460 | to moving your mouth, that is chewing,

00:43:38.260 | which makes perfect sense when you hear it, right?

00:43:40.660 | One way to suppress appetite is to sew the jaw shut neurally,

00:43:44.820 | or at least make it less likely to open your mouth

00:43:47.060 | and put food in it.

00:43:48.660 | Actually, that reminds me of a story.

00:43:50.180 | I'll just interrupt myself to tell a brief story.

00:43:52.380 | That there's a famous Nobel Laureate who won

00:43:54.580 | the Nobel Prize for something totally distant from appetite,

00:43:57.060 | but once turned to a friend of mine at a meeting and said,

00:44:00.540 | I discovered the biological mechanism for losing weight.

00:44:06.440 | And my friend said, well, of course, it's a, you know,

00:44:09.720 | ingest fewer calories than you burn, right?

00:44:11.340 | Calories in, calories out.

00:44:12.260 | Fundamental rule of thermodynamics

00:44:13.920 | and basically the fundamental rule of weight loss,

00:44:16.180 | weight gain, or weight maintenance.

00:44:18.100 | And he said, no, it's actually the gene that controls

00:44:22.020 | whether or not you open your mouth.

00:44:23.900 | Now he was making a very nerdy joke.

00:44:25.800 | So if you didn't register that as a joke,

00:44:27.520 | that's about as funny as neuroscience or biology jokes get.

00:44:30.900 | There are a couple of funnier ones,

00:44:31.780 | but that one's kind of considered on the funnier side.

00:44:33.620 | So this is why we're not considered comedians.

00:44:36.480 | But the point of the matter is that whether or not you crave

00:44:41.480 | or desire or impulsively want to put things in your mouth

00:44:45.040 | and chew it will actually dictate

00:44:46.360 | how many calories that you eat.

00:44:47.740 | And so I find it remarkable and indeed important to know

00:44:50.460 | that these POMC neurons are actually inhibiting the opening

00:44:53.520 | and the movement of the mouth for chewing.

00:44:55.140 | So when we smoke or when we ingest nicotine

00:44:57.220 | in any other way, you activate these POMC neurons,

00:44:59.760 | you suppress appetite, but in part, you do that

00:45:01.900 | by actually limiting the impulse to chew.

00:45:04.280 | Incredible, at least to me.

00:45:05.900 | Now, in addition to limiting appetite

00:45:08.100 | by changing one's desire to ingest food and chew it

00:45:11.340 | and actual craving of food

00:45:13.420 | by regulation of blood sugar, et cetera,

00:45:15.380 | there do seem to be some quite direct effects

00:45:18.500 | of nicotine on metabolism.

00:45:21.180 | And the effects on metabolism aren't enormous.

00:45:23.300 | These are increases in metabolism that are about 2%

00:45:27.220 | up to about 5%, but I want to emphasize

00:45:30.340 | that those are transient increases in metabolism.

00:45:33.900 | Nonetheless, people that quit smoking

00:45:36.660 | often find that their appetite goes up.

00:45:38.560 | They sometimes gain weight, they sometimes do not,

00:45:40.640 | depending on whether or not they offset

00:45:42.420 | that increase in appetite with increased physical exercise

00:45:45.060 | or with decreased food intake in other ways.

00:45:47.300 | But there does seem to be this direct effect

00:45:49.040 | of ingesting nicotine on metabolism,

00:45:51.060 | which I find is interesting

00:45:52.460 | because if you look in the literature,

00:45:53.900 | one of the reasons why people are reluctant

00:45:57.020 | to quit ingesting nicotine, if for instance,

00:46:00.500 | they want to quit using the delivery device

00:46:04.000 | to nicotine that's causing such problems for their health,

00:46:06.280 | like smoking or vaping,

00:46:08.060 | or whether or not they find themselves quote unquote

00:46:11.340 | addicted to or have the habit of ingesting nicotine,

00:46:15.440 | in part that's likely due to be the dopamine effects, right?

00:46:19.060 | Because dopamine is highly reinforcing and rewarding.

00:46:21.140 | It feels good, so people want to do more of it.

00:46:23.340 | But it's also that for many people,

00:46:25.540 | and here the data really points to the fact

00:46:27.140 | that a lot of the younger female smokers

00:46:29.620 | or younger female vapers,

00:46:32.540 | or when I say that, of course,

00:46:34.180 | I mean younger females that vape are doing that

00:46:38.840 | because they like the appetite suppressing effects,

00:46:41.260 | which of course opens up an entire conversation

00:46:43.300 | about the sociology of body imagery, et cetera,

00:46:46.260 | a topic for a future podcast.

00:46:47.940 | Okay, so nicotine has certain effects on the brain

00:46:50.940 | by virtue of the fact that nicotine binds

00:46:54.340 | these nicotinic acetylcholine receptors,

00:46:56.360 | and those receptors are found on some,

00:46:58.060 | but not all neural circuits within the brain.

00:47:00.180 | And we talked about some of them already,

00:47:01.980 | mesolimbic, the POMC neurons, et cetera.

00:47:04.340 | Now, when we ingest nicotine,

00:47:05.880 | it goes from the bloodstream to all the tissues

00:47:09.660 | and organs of the body.

00:47:10.740 | How does it do that, right?

00:47:11.920 | I mean, amazing.

00:47:12.760 | It can pass to everything, the brain, the body.

00:47:15.600 | It does that because nicotine is fat soluble.

00:47:19.020 | And now when anytime people hear the word fat,

00:47:20.860 | they tend to think about body fat, subcutaneous fat,

00:47:23.660 | or maybe they think about dietary fat.

00:47:25.820 | What I mean by fat soluble in the context

00:47:27.780 | of nicotine being fat soluble is that the cells

00:47:31.540 | of your body have an outer layer, so-called outer membrane,

00:47:35.620 | and it's made up of lipid, of fat,

00:47:37.760 | very particular types of lipids, in fact.

00:47:39.820 | Nicotine has this remarkable ability

00:47:42.860 | to move through that fatty tissue.

00:47:46.640 | Not all molecules have that ability, but nicotine does.

00:47:50.320 | So it can move relatively freely through the brain and body

00:47:53.180 | and relatively freely from outside of cells,

00:47:56.200 | extracellular space to intracellular space.

00:47:59.240 | So it can get into cells.

00:48:00.380 | It can do that with the brain.

00:48:01.260 | We talked about those effects,

00:48:02.300 | and it can do that within the body.

00:48:04.180 | Now, anytime we're talking about the body,

00:48:06.260 | we can be talking about any number of things,

00:48:07.780 | but today I'm going to refer to the periphery

00:48:10.060 | and the body in more or less the same way,

00:48:11.820 | but keep in mind in the back of your head, pun intended,

00:48:15.700 | you have your brain, your eyes, and the spinal cord,

00:48:20.100 | and those three things make up your central nervous system.

00:48:22.740 | The peripheral nervous system and the periphery,

00:48:24.700 | which is the rest of your body,

00:48:26.100 | that contain your organs and so forth

00:48:27.860 | outside of the nervous system,

00:48:29.540 | things like your liver and your stomach, et cetera,

00:48:31.700 | that's what we're going to talk about now,

00:48:33.540 | because nicotine has profound effects

00:48:36.220 | on the organs of the body that are separate from,

00:48:38.760 | but that occur in parallel at the same time

00:48:41.540 | as the effects of nicotine on the brain.

00:48:44.080 | So let's talk about what some of those effects are.

00:48:46.040 | When nicotine makes it into the bloodstream,

00:48:47.740 | again, within two to 15 minutes of ingesting it,

00:48:50.100 | depending on the delivery device,

00:48:52.740 | your heart rate will increase,

00:48:55.620 | blood pressure will increase,

00:48:57.540 | and the contractibility of the heart tissue

00:49:00.100 | will actually increase.

00:49:01.880 | So what that essentially speaks to

00:49:04.740 | is an increase in so-called sympathetic tone.

00:49:07.180 | And when I say that, I don't mean an increase in sympathy

00:49:09.660 | for others of the emotional sort.

00:49:11.440 | What I mean is an increase in the sympathetic activity

00:49:15.700 | of the sympathetic arm of the autonomic nervous system,

00:49:18.020 | which is a real mouthful and mindful of ideas,

00:49:21.540 | but all you need to know is that it's a generalized system

00:49:24.760 | that increases levels of alertness and physical readiness.

00:49:28.600 | So it makes you ready for action,

00:49:29.820 | makes you ready for thought.

00:49:31.520 | It's balanced by a whole other system

00:49:33.300 | called the parasympathetic nervous system,

00:49:35.180 | which is basically the so-called rest and digest system,

00:49:38.040 | which is a system of neurons and organs, et cetera,

00:49:40.600 | that put your body and your brain into a state

00:49:43.060 | of not being able to think clearly,

00:49:45.180 | to digest and to fall asleep, okay?

00:49:47.180 | So nicotine increases heart rate,

00:49:49.620 | blood pressure and contractibility of the heart.

00:49:51.560 | So it's going to cause more blood flow in theory,

00:49:54.540 | although it also tends to constrict blood vessels

00:49:58.020 | in many locations in the body.

00:49:59.660 | This explains the decrease in penile girth effect

00:50:03.080 | of nicotine, in particular nicotine ingested

00:50:05.780 | by smoking or vaping.

00:50:07.300 | That's right, smoking and vaping reduces penis size

00:50:11.540 | and also will have damaging effects

00:50:14.740 | on the blood lining endothelial tissue.

00:50:18.140 | So over time, it actually is impairing blood's ability

00:50:20.740 | to get to the penis chronically,

00:50:23.240 | as well as to other organs of the body.

00:50:25.180 | But when people ingest nicotine acutely,

00:50:27.800 | and let's say they do that by Nicorette patch

00:50:30.260 | or by toothpick dipped in nicotine,

00:50:32.420 | it will have some of these same effects,

00:50:34.460 | but when not smoking tobacco,

00:50:37.420 | when bringing nicotine into the bloodstream

00:50:39.260 | through other mechanisms,

00:50:40.800 | many, if not all of the disruption

00:50:42.580 | of the endothelial cell function can be bypassed.

00:50:46.000 | But the effects on penile girth,

00:50:49.340 | the effects on reducing blood flow to various tissues

00:50:52.040 | is still present during the effects of nicotine,

00:50:55.340 | which as I mentioned, last about one to two hours.

00:50:57.520 | The half-life is about one to two hours,

00:50:59.200 | depending on a number of factors.

00:51:00.780 | Not interesting for today's discussion.

00:51:03.120 | So when nicotine gets into the bloodstream,

00:51:05.440 | it's making us more alert.

00:51:06.840 | It's preparing our body for readiness.

00:51:08.780 | The heart is pumping harder.

00:51:10.220 | Epinephrine, that is adrenaline,

00:51:13.080 | is released from the adrenal glands,

00:51:14.740 | which ride atop our kidneys.

00:51:16.820 | So everything is pointed toward creating more readiness

00:51:20.700 | to move, more readiness to think.

00:51:22.860 | And again, this is happening in parallel

00:51:24.260 | with all the effects of neurochemistry

00:51:26.180 | that are happening with the brain

00:51:27.160 | that we talked about a few minutes ago.

00:51:29.700 | Now what's interesting about nicotine

00:51:31.420 | is that while it causes this global increase in readiness

00:51:34.460 | and alertness and attention and mood, et cetera,

00:51:37.180 | it also has the effect of somewhat relaxing skeletal muscle.

00:51:42.020 | Now that might seem counterintuitive

00:51:43.480 | to those of you out there

00:51:44.460 | that already know what I'm about to tell

00:51:46.380 | the rest of you who didn't know it previously,

00:51:49.520 | that your muscles are able to contract

00:51:53.220 | because of the effects of acetylcholine

00:51:56.500 | released from neurons in your spinal cord

00:51:59.660 | that spit out acetylcholine onto the muscle

00:52:02.420 | and bind to what?

00:52:04.260 | Nicotinic acetylcholine receptors.

00:52:06.160 | Put into plain English,

00:52:07.820 | nicotinic receptors are also the ways

00:52:10.500 | in which your muscles can get activated.

00:52:12.700 | So therefore, why would it be that increasing nicotine

00:52:15.260 | would cause relaxation of the muscles?

00:52:17.780 | And that has to do with some of the neural circuits

00:52:19.900 | that are upstream of the muscles

00:52:21.340 | and it has to do with a little bit

00:52:22.480 | of how the autonomic nervous system is arranged

00:52:24.820 | in terms of which receptors go where.

00:52:26.500 | A topic and kind of rabbit hole of conversation

00:52:30.100 | far too deep for right now,

00:52:31.340 | at least in the context of this already

00:52:32.900 | somewhat detailed discussion of the effects of nicotine.

00:52:35.900 | But if we were to zoom out

00:52:37.780 | and just think about the effects of nicotine,

00:52:39.760 | we now have a very clear picture.

00:52:42.200 | Reward pathways are turned on.

00:52:44.520 | Attention is turned on.

00:52:45.680 | Alertness is turned on.

00:52:47.560 | You feel better than you felt a few minutes ago.

00:52:49.920 | Your blood pressure is up.

00:52:52.560 | Your heart rate is up.

00:52:54.560 | Your preparedness for thinking is elevated as well.

00:52:59.440 | And yet your body is somewhat relaxed.

00:53:02.560 | That's a very interesting state of mind and body.

00:53:06.040 | Interesting because it's somewhat ideal for cognitive work.

00:53:11.360 | Like if you were going to sit down and work on a book

00:53:13.560 | or you're going to sit down

00:53:14.400 | and try and figure out a hard math problem,

00:53:16.300 | or you're going to write a letter

00:53:17.340 | that's been really challenging for you to write,

00:53:19.080 | or maybe that you're really excited to write,

00:53:21.700 | but that you've been slow to get out the door

00:53:24.020 | for whatever reason here,

00:53:24.860 | I'm talking about my own habits of procrastination.

00:53:27.480 | Well, that state of being very alert

00:53:29.480 | but your body being relaxed is almost,

00:53:32.360 | if not the optimal state for getting mental work done.

00:53:36.300 | Because if you're feeling agitated in your body

00:53:38.240 | and you want to physically move your body,

00:53:39.480 | it's very hard to do cognitive work,

00:53:40.760 | at least the sorts of cognitive work

00:53:42.060 | that involve typing or writing or these sorts of things.

00:53:45.180 | It's also the exact opposite of the optimal state

00:53:48.320 | for physical performance,

00:53:49.640 | which is one of, yes, also alertness.

00:53:53.480 | Yes, also motivation and elevated mood.

00:53:55.700 | That's all wonderful stuff to have in mind, literally,

00:53:59.400 | when you are exercising or competing in sport

00:54:01.880 | or something of that sort.

00:54:03.440 | But under those conditions,

00:54:04.600 | you really also want to have a fast reaction time,

00:54:08.160 | a low latency for muscle activation

00:54:09.960 | so that you can make coordinated muscle movements

00:54:11.520 | in the ways that you need to,

00:54:12.920 | which is of course what's required of physical endeavors.

00:54:15.680 | That tells us a few things.

00:54:16.680 | First of all, it tells us that nicotine

00:54:18.380 | is going to be generally a bad idea

00:54:21.480 | for a pre-workout tool

00:54:24.920 | or for enhancing physical performance.

00:54:28.340 | However, it's apt to be, and in fact is,

00:54:31.360 | an excellent tool for enhancing cognitive ability.

00:54:34.420 | And of course, that triggers my mind

00:54:36.400 | to return to the anecdote

00:54:37.560 | about my Nobel Prize winning colleague

00:54:39.400 | who ingests nicotine by way of nicotine-containing gum

00:54:42.920 | in order to increase levels of cognitive focus,

00:54:45.440 | certainly not for going out and playing sport.

00:54:47.520 | In fact, despite the fact that he is very, very tall,

00:54:50.940 | he often points to himself in an appropriately funny way

00:54:55.880 | that despite being on the basketball team of his high school,

00:54:58.720 | he's probably the worst player that ever existed

00:55:00.960 | and they only positioned him there because of his height.

00:55:02.800 | And I guess his head was designed to prevent balls

00:55:06.040 | from entering the basket.

00:55:07.320 | In any event, nicotine does seem to be very good

00:55:10.960 | at enhancing cognitive function, at least in the short term,

00:55:14.440 | which is not to say that it isn't without its side effects,

00:55:16.680 | which we will talk about.

00:55:17.960 | And again, those are side effects

00:55:19.000 | that are independent of smoking or vaping

00:55:20.920 | or other forms of ingesting nicotine.

00:55:23.480 | For instance, dipping or chewing tobacco

00:55:27.500 | is known to cause a 50-fold, yes, five-zero,

00:55:30.640 | 50-fold increase in mouth cancers, things like leukoplakia,

00:55:34.560 | and just generally is terrible for your health.

00:55:37.420 | I'm sorry to break it to you, but if you're dipping

00:55:39.960 | or you're using snuff or things of that sort,

00:55:42.480 | certainly I'm not going to tell people what to do.

00:55:44.320 | That's not my role in life,

00:55:46.440 | but you are dramatically increasing the probability

00:55:49.720 | of an oral cancer or of a mucosal lining cancer

00:55:52.800 | of some sort.

00:55:54.100 | So it's not just that smoking and vaping

00:55:56.040 | are bad for your health.

00:55:56.880 | These other forms of delivery from nicotine

00:55:58.660 | can be bad for your health as well.

00:56:00.080 | And whether or not ingesting nicotine

00:56:01.520 | by way of nicotine-containing gum or patch

00:56:04.400 | or toothpick or other method is dangerous.

00:56:07.800 | For other reasons is a discussion that's important.

00:56:10.400 | Right now, it appears that provided

00:56:12.760 | the dosages are kept reasonable,

00:56:16.720 | and we'll talk about what reasonable means a little later,

00:56:18.820 | and the frequency is kept relatively low,

00:56:21.640 | so not relying on these things constantly,

00:56:24.360 | there may in fact be some benefit

00:56:26.080 | to ingesting nicotine from time to time,

00:56:27.700 | provided that you are not still developing your brain.

00:56:32.360 | Now, in reality, neuroplasticity goes on

00:56:34.440 | throughout the lifetime.

00:56:35.960 | Your life is actually one long developmental arc.

00:56:37.860 | It's not like development occurs and then stops.

00:56:40.240 | But certainly for people before puberty, during puberty,

00:56:43.160 | and probably for the next 15 to 20 years after puberty,

00:56:47.200 | avoiding nicotine is probably a good idea.

00:56:49.800 | Now, of course, development is your entire life.

00:56:52.200 | It's not like development starts and then ends,

00:56:53.780 | but certainly for people that are 25 years old or younger,

00:56:58.120 | ingesting nicotine as a way to enhance cognitive function

00:57:00.800 | is probably not the best idea.

00:57:02.400 | And certainly, please, for those of you

00:57:05.060 | that are 15 years old or younger,

00:57:07.360 | ingesting nicotine in any form,

00:57:09.120 | unless it's prescribed by your doctor

00:57:10.560 | for a very specific clinical reason,

00:57:13.160 | to me seems just like a terrible idea

00:57:15.240 | based on all the data that I've read.

00:57:17.000 | And the reason for that is it's going to create a scenario

00:57:19.720 | of nicotine dependence in order to achieve

00:57:21.740 | heightened levels of mood and alertness, et cetera.

00:57:24.320 | And that's bad.

00:57:25.240 | And what we're effectively talking about

00:57:26.500 | is an addiction for nicotine directly,

00:57:28.420 | not necessarily the delivery device method

00:57:30.720 | like smoking or vaping, although it could pull that in

00:57:33.200 | as an addictive or habit-forming behavior as well.

00:57:35.760 | But you want to let your neural circuits develop

00:57:37.800 | to the point where, again, unless there's a clinical need

00:57:41.000 | for a prescribed drug from a licensed physician

00:57:42.880 | or psychiatrist, et cetera, that you're not relying

00:57:46.100 | on chemical enhancement of these circuits.

00:57:48.580 | For people who are 25 years or older,

00:57:53.440 | and again, that's not a strict cutoff,

00:57:54.800 | but roughly 25 years or older,

00:57:56.680 | but for those of you that are thinking about using nicotine

00:58:00.120 | to enhance cognitive function as adults

00:58:03.000 | and your brain development is slowing down, right?

00:58:06.040 | Never ceases, but it's slowing down or has slowed down

00:58:09.380 | to the point where we would say developmental plasticity

00:58:12.120 | is largely over and you're now operating

00:58:14.280 | in the context of adult neuroplasticity.

00:58:17.880 | Well, in that case, there may be instances

00:58:20.000 | in which increasing acetylcholine, dopamine, et cetera,

00:58:24.020 | by way of nicotine ingestion might be a good idea,

00:58:26.940 | but certainly not by smoking, vaping,

00:58:28.880 | or by direct contact of tobacco

00:58:31.500 | to the mucosal lining tissue of the mouth or nose,

00:58:34.140 | so-called dipping or snuffing.

00:58:35.660 | For the last 20 minutes or so,

00:58:37.000 | we've been talking about the biology

00:58:38.340 | of nicotine specifically, how it impacts the brain,

00:58:40.780 | how it impacts the body, why it feels so good,

00:58:42.960 | why it can enhance focus.

00:58:44.480 | And we've largely set aside smoking, vaping,

00:58:48.820 | dipping tobacco, and snuffing, and the negative effects

00:58:52.640 | that those all have on mental and physical health.

00:58:55.560 | Working down from the top of the head

00:58:56.880 | to the bottom of the feet, we can say that smoking,

00:59:00.080 | vaping, dipping, and snuffing

00:59:02.920 | negatively impact every organ and tissue system

00:59:05.380 | and cell of the body by virtue of the fact

00:59:08.200 | that they all damage the endothelial cells.

00:59:11.360 | Again, the endothelial cells are the cells

00:59:13.080 | that make up the vasculature,

00:59:14.680 | which delivers blood and other nutrients

00:59:18.120 | to all the cells and organs and tissues of the body.

00:59:21.040 | And those endothelial cells are strongly

00:59:23.760 | and negatively impacted by all of the practices

00:59:26.580 | that I just described.

00:59:28.280 | Now, the way that that happens varies a little bit

00:59:30.000 | from each one to the next.

00:59:31.040 | For instance, it has been estimated

00:59:33.840 | that cigarettes contain anywhere

00:59:35.520 | from 4,000 to 7,000 toxins.

00:59:38.400 | Now, the word toxins is a real buzzword these days.

00:59:40.380 | You hear about detoxes and toxins.

00:59:42.720 | But more specifically, we know that it contains carcinogens.

00:59:46.880 | These are cancer-promoting compounds.

00:59:49.360 | For instance, we know that the tar in cigarettes,

00:59:52.120 | even low-tar cigarettes,

00:59:53.720 | as well as the ammonia within cigarettes,

00:59:55.700 | as well as the formaldehyde contained within cigarettes,

00:59:58.780 | as well as the carbon dioxide that's generated

01:00:00.840 | from smoking those cigarettes are all carcinogens.

01:00:04.000 | Carbon dioxide also has the negative effect

01:00:06.440 | of depleting the amount of oxygen that's delivered

01:00:08.760 | to any and all of our tissues

01:00:10.440 | by way of the impact of carbon dioxide,

01:00:14.000 | binding hemoglobin and preventing hemoglobin

01:00:16.640 | from delivering oxygen to the tissues of the body.

01:00:19.440 | So while there may be 4,000 or 4,500 or 7,000 toxins,

01:00:23.440 | depending on which cigarette,

01:00:24.600 | which papers they happen to be rolled in,

01:00:26.520 | whether or not they're filtered or non-filtered,

01:00:28.320 | the type of tobacco, et cetera, et cetera,

01:00:30.880 | there are a tremendous number of toxins

01:00:33.440 | and there are some very potent carcinogens

01:00:35.820 | within that long list of toxins.

01:00:37.860 | Again, ammonia, tar, formaldehyde, and carbon dioxide

01:00:41.060 | being the most potent of those carcinogens.

01:00:43.640 | Now, the fact that there are carcinogens in cigarettes

01:00:45.640 | sometimes lead cigarette smokers,

01:00:47.080 | and particularly the cigarette smokers

01:00:48.960 | that have the hardest time quitting

01:00:50.340 | or that enjoy their cigarettes the most from saying,

01:00:52.320 | "Well, listen, everything is a carcinogen,"

01:00:54.320 | or, "Everything kills you."

01:00:55.160 | Well, certainly that's not a true statement.

01:00:58.840 | And while there are other carcinogens in the environment,

01:01:01.480 | so environmental hazards like solvents,

01:01:04.360 | and even if you work in a laboratory, for instance,

01:01:07.100 | we use in the laboratory DNA intercalating dyes.

01:01:09.860 | These are literally dyes that allow us

01:01:11.400 | to see the DNA structure of cells

01:01:13.180 | and see the proteins they make

01:01:14.520 | and see the RNAs they make.

01:01:16.160 | And it's very important to wear gloves

01:01:17.480 | when you work with those things,

01:01:18.360 | because as the name suggests, they intercalate,

01:01:20.440 | they actually get in between the strands of DNA

01:01:22.560 | and separate them.

01:01:23.660 | They are mutagens, they mutate DNA.

01:01:26.160 | They are often carcinogens as well.

01:01:27.820 | So we have them in our laboratory,

01:01:29.120 | but we take certain precautions

01:01:30.400 | to not have them negatively impact our health,

01:01:32.560 | safety protocols, and so on.

01:01:34.100 | We hear that there are carcinogens in car exhaust

01:01:38.140 | and bus exhaust and in all sorts of things like pesticides,

01:01:41.040 | and that's all true.

01:01:42.260 | So in the argument of probabilities, one would say,

01:01:44.960 | "Well, if there are all these other carcinogens

01:01:47.440 | in the environment, why would you compound

01:01:49.980 | their carcinogenic effect by smoking or vaping

01:01:52.960 | or dipping or snuffing?"

01:01:54.460 | But that usually doesn't get people to quit smoking

01:01:56.360 | or doing those things because of the powerful

01:01:57.860 | reinforcing effects of nicotine itself.

01:02:00.140 | So again, nicotine is the reinforcing element

01:02:02.920 | by way of triggering that dopamine reinforcement pathway,

01:02:06.000 | the mesolimbic reward pathway.

01:02:07.700 | And of course, there are all the other additional effects

01:02:11.380 | of increased focus, such as increased ability

01:02:14.500 | to pay attention to work or to others

01:02:16.280 | that lead to other rewards.

01:02:17.560 | And so then it becomes a situation of compounding rewards.

01:02:19.960 | So it's not really about the cigarette,

01:02:21.460 | it's about the nicotine,

01:02:22.380 | and it's not really about the nicotine,

01:02:23.580 | it's about the dopamine that the nicotine evokes.

01:02:25.580 | And then it's not really about the dopamine

01:02:27.180 | that the nicotine evokes directly per se,

01:02:30.000 | but also about all the positive effects

01:02:31.800 | that that increased dopamine results in.

01:02:34.500 | So we can easily circle back to the negative effects

01:02:37.140 | of smoking, vaping, dipping, and snuffing,

01:02:40.180 | and say the endothelial cells are disrupted.

01:02:43.540 | The endothelial cells are involved in delivery of blood

01:02:46.060 | and other nutrients to every tissue of the body,

01:02:48.300 | and smoking, vaping, dipping, and snuffing

01:02:51.020 | contain carcinogens, which are cancer promoting.

01:02:53.540 | And because the epidemiological studies are out there,

01:02:55.780 | we can actually arrive at some very clear numbers

01:02:58.040 | as to how much life one will lose

01:03:01.400 | from ingesting nicotine by way

01:03:04.120 | of those four delivery devices,

01:03:06.160 | or I should say any one of those four delivery devices.

01:03:09.380 | Although I should also mention that many people

01:03:11.260 | who are vaping are also smoking cigarettes,

01:03:13.280 | this is becoming increasingly common.

01:03:14.740 | A lot of people are using vaping in one context

01:03:16.820 | and cigarettes in another,

01:03:18.000 | dipping in one context, vaping in another.

01:03:20.060 | But even for those that only smoke, or only vapor,

01:03:23.160 | only dip, or only snuff,

01:03:25.440 | the negative effects are dramatic and calculable.

01:03:30.020 | So it is thought that for every pack of cigarettes

01:03:32.900 | consumed per day, so you could average that out

01:03:35.560 | if you're a two a day cigarette smoker,

01:03:37.940 | or a pack a day cigarette smoker, or two pack a day,

01:03:41.500 | for every pack of cigarettes smoked per day,

01:03:45.720 | we can reliably estimate a 14 year reduction in lifespan.

01:03:50.720 | So cigarettes are literally peeling years off your life.

01:03:55.120 | Now, because of the way that the brain works

01:03:57.000 | and the way that human beings anticipate the future

01:04:00.480 | and can be grounded both in the present and the future,

01:04:03.800 | or the present and the past,

01:04:04.920 | that's just how the mind works, right?

01:04:06.160 | That's why we can think about the future,

01:04:07.500 | but also realize where we are in time and space today.

01:04:10.500 | Because of that, many people will say,

01:04:11.800 | well, I enjoy cigarettes, or I enjoy vaping,

01:04:15.040 | and so at least while I'm here, I'm enjoying it.

01:04:16.560 | And that's because the dopamine system is not very good

01:04:19.640 | at understanding opportunity costs.

01:04:22.720 | That is what we would be doing in those 14 years,

01:04:25.480 | and what we would be enjoying,

01:04:26.740 | and the enrichment that we would get

01:04:28.440 | if we were to live into those 14 years.

01:04:30.680 | So at some level, the smoker, the vapor is being rational

01:04:33.720 | when they say, yeah, but I enjoy this.

01:04:35.720 | And so the years lost, I can't really register that

01:04:39.240 | because it's hard to register what you don't have

01:04:41.080 | and what you've never had, right?

01:04:43.040 | On the other hand, we can also point to the statistic

01:04:46.480 | that there is this 50-fold increase

01:04:49.000 | in mouth cancers from dipping,

01:04:51.240 | and there are nasal cancers as well

01:04:53.400 | that are greatly increased by snuffing,

01:04:56.280 | and from smoking, and now we know based on data from vaping,

01:05:01.280 | that the endothelial cell damage and the direct effects

01:05:05.520 | of damage to the lungs from TARS,

01:05:07.320 | and even if people are vaping,

01:05:08.740 | which tends to have lower TARS than do cigarettes,

01:05:11.920 | even for people that are vaping,

01:05:13.640 | greatly increased probability of stroke,

01:05:17.080 | of peripheral vascular disease.

01:05:18.760 | So this is peripheral pain because remember,

01:05:21.240 | blood is delivering not just blood, but other nutrients,

01:05:23.940 | and it's clearing things out from tissues.

01:05:26.300 | So there's an accumulation of literally toxins and debris

01:05:29.440 | that cells generate all the time, which is healthy,

01:05:31.660 | but then normally is cleared away by the endothelial cells

01:05:35.300 | and by other cell types of the immune system.

01:05:38.120 | That's all increased in people

01:05:40.600 | that engage in these nicotine delivery device behaviors.

01:05:43.700 | Rates of heart attack, rates of stroke,

01:05:47.120 | rates of cognitive decline are all increased.

01:05:49.920 | Now you might say cognitive decline,

01:05:51.000 | I thought that nicotine increases the likelihood

01:05:54.120 | that we can maintain healthy neuronal function

01:05:56.160 | and cognitive capacity.

01:05:57.480 | It might even increase cognitive capacity in a potent way

01:06:00.120 | in the short term, and indeed it does.

01:06:01.880 | However, cigarette smoking and vaping

01:06:05.460 | are now known to dramatically decrease cognitive function

01:06:10.080 | because one of the key things about the brain

01:06:12.320 | is that it is the most metabolically demanding organ,

01:06:15.040 | which means it consumes a lot of glucose,

01:06:16.640 | or even if you're ketogenic, you need ketones.

01:06:18.800 | You need nutrients getting to the neurons

01:06:20.640 | and other cell types of the brain and nervous system

01:06:22.760 | in order for it to function properly.

01:06:24.400 | And when you disrupt the vasculature

01:06:26.280 | through this endothelial cell dysfunction,

01:06:28.700 | you got things like interstitial,

01:06:30.200 | which just means in the spaces between dysfunction.

01:06:32.420 | So it's not just beating up the endothelial cells themselves,

01:06:35.560 | but the spaces between the cells is being disrupted.

01:06:38.160 | There's a lot of debris that accumulates there.

01:06:39.920 | And as a consequence,

01:06:41.520 | the brain just simply will not function as well.

01:06:44.360 | So you start getting short-term memory lapses,

01:06:46.280 | you start getting working memory lapses.

01:06:47.800 | Working memory is a sort of memory,

01:06:49.280 | if someone tells you their seven digit phone number,

01:06:52.500 | typically nowadays people just share their info,

01:06:54.400 | but seven digit phone number or a sequence of numbers

01:06:56.720 | or an address and your inability to remember that.

01:06:58.720 | So you're walking back to the kitchen sink

01:07:00.140 | and you can't remember what you were trying to remember

01:07:02.440 | just a short moment ago, that's working memory.

01:07:04.540 | Working memory suffers long-term memory,

01:07:07.320 | projective or interrogating memories into the future.

01:07:10.480 | How can you remember things in the future

01:07:13.560 | that haven't occurred yet?

01:07:14.440 | Well, this is more of a memory for future plans

01:07:17.400 | or ideas and planning for things that are to come.

01:07:20.680 | So what we can very reliably say is that currently

01:07:23.240 | more than 1 billion, billion,

01:07:25.760 | more than 1 billion people consume tobacco

01:07:29.240 | in order to get their nicotine,

01:07:30.940 | 'cause that's really the reinforcing element within tobacco.

01:07:35.080 | More than 1 billion people consume tobacco

01:07:37.360 | in the form of cigarettes every day.

01:07:41.000 | A growing number of people,

01:07:42.720 | more than half a billion people now are starting to vape.

01:07:46.920 | The estimates range from 200 million to 500 million.

01:07:50.520 | And there's a lot of debate about this

01:07:51.980 | because a lot of people are hybrid smokers and vapers,

01:07:54.920 | meaning they do one or both,

01:07:57.000 | depending on time of day and location,

01:07:58.520 | as I mentioned before.

01:07:59.880 | But now you start to see how you can get to the number

01:08:04.120 | that billions of people are consuming tobacco,

01:08:06.480 | because of course you also have your people

01:08:08.200 | that are dipping and your people that are snuffing.

01:08:10.360 | And as I mentioned before,

01:08:11.280 | you have people that are engaging

01:08:12.840 | in multiple of these behaviors.

01:08:15.520 | So billions of people on planet earth,

01:08:18.540 | anywhere from one eighth to a quarter of human beings,

01:08:22.480 | incredible, right?

01:08:23.960 | Anywhere from one eighth to a quarter of human beings

01:08:26.160 | are consuming tobacco in one form or another

01:08:28.800 | in order to get their nicotine one way or another.

01:08:32.740 | And as a consequence are peeling years off their life,

01:08:36.560 | dramatically increasing the probability of cancer,

01:08:39.300 | stroke, heart attack, peripheral neuropathies,

01:08:43.480 | brain dysfunction, meaning cognitive dysfunction,

01:08:46.560 | memory impairment, sexual dysfunction.

01:08:49.840 | There are a number of studies

01:08:50.680 | that have looked at increases in cortisol.

01:08:52.680 | And while minor, those increases do exist,

01:08:55.680 | decreases in growth hormone.

01:08:57.160 | And while minor, those decreases exist.

01:09:00.260 | But even setting aside the negative impact on endocrine,

01:09:05.040 | on hormone factors, it's very, very clear

01:09:08.460 | that smoking, vaping, dipping and snuffing

01:09:13.000 | are among the worst things that we can do for our health.

01:09:16.480 | They are among the leading causes of preventable death

01:09:19.720 | and debilitating life conditions,

01:09:21.860 | which may lead you to the question

01:09:24.800 | as to why in the world would people do this?

01:09:29.000 | Well, it turns out most of them don't want to.

01:09:32.980 | In the best surveys that one can find

01:09:35.120 | of if you could quit smoking,

01:09:37.540 | if you could quit vaping, would you?

01:09:39.940 | What you find is that at least for cigarette smokers,

01:09:43.240 | 70%, seven zero, want to quit.

01:09:47.540 | They would love to quit.

01:09:49.180 | And yet they find that to be exceedingly difficult.

01:09:52.040 | And the reason they find it to be exceedingly difficult

01:09:54.520 | is because of all the brain neurochemistry

01:09:56.600 | that we talked about before.

01:09:57.520 | The reason I spent close to 20 minutes

01:09:59.400 | talking about dopamine and the mesolimbic pathway,

01:10:01.980 | acetylcholine and nucleus basalis,

01:10:04.440 | and epinephrine and the relaxation of muscles

01:10:08.000 | in the periphery and the increase in readiness

01:10:09.920 | in the body and brain is that all of those combine

01:10:13.780 | to make nicotine one of the most powerful

01:10:15.800 | and potent cognitive enhancers,

01:10:17.640 | and to some extent, physical enhancer.

01:10:19.800 | Although, as I mentioned before,

01:10:21.520 | the total number of physical exercise

01:10:25.000 | or physical sport promoting effects of nicotine

01:10:28.640 | is very, very small, if not zero.

01:10:31.740 | There are certain conditions

01:10:33.160 | under which one might imagine using nicotine

01:10:36.140 | specifically for cognitive enhancement

01:10:37.900 | where performance of complex motor skills

01:10:41.400 | would sort of outweigh the negative effects

01:10:43.880 | on the neuromuscular system,

01:10:45.060 | our ability to generate coordinated movements.

01:10:47.720 | There's actually an excellent study

01:10:49.260 | looking at the effects of nicotine,

01:10:51.280 | not by smoking delivery,

01:10:52.560 | but by a different delivery mechanism

01:10:55.120 | in which they looked at performance of hitters in baseball.

01:10:59.440 | The experiment was kind of an interesting one.

01:11:01.180 | Even though these were fairly skilled baseball players,

01:11:03.340 | what they had them do was hit a ball off a tee.

01:11:05.840 | As I recall growing up,

01:11:07.320 | and admittedly, I didn't play much baseball,

01:11:09.640 | but you start off on tee ball and then you would go,

01:11:12.040 | I think it was to pitching machine,

01:11:13.280 | then they would use actual pitchers who throw the ball.

01:11:15.400 | But in this case,

01:11:16.440 | it was a couple of different baseball-related tasks.

01:11:19.200 | They'd have people hit the ball off a tee,

01:11:21.740 | but they had to direct that hit

01:11:23.520 | toward a ball atop another tee.

01:11:25.800 | So it's fairly precise targeting that's required

01:11:28.080 | in order to knock that ball off the other tee.

01:11:30.000 | So this is an activity that involves not just motor output,

01:11:32.680 | but coordinated motor output,

01:11:34.440 | and not just coordinated motor output,

01:11:36.680 | but directed coordinated output that requires some,

01:11:40.640 | as we would say, top-down processing, right?

01:11:42.480 | This isn't the kind of thing that can be done reflexively.

01:11:44.820 | This is the kind of thing where the forebrain,

01:11:47.280 | the prefrontal cortex in particular,

01:11:48.640 | has to be heavily involved

01:11:49.740 | in order to suppress certain actions

01:11:51.660 | and then create other actions.

01:11:53.220 | So the basic takeaway of the study

01:11:54.640 | is that nicotine delivered by way of nicotine gum,

01:11:57.960 | not by smoking, dipping, or snuffing,

01:12:00.160 | was able to increase cognitive performance and motor output.

01:12:04.280 | So a rare circumstance where a specific set of demands

01:12:08.980 | that involve both cognitive engagement

01:12:11.480 | and physical engagement showed a slight,

01:12:13.860 | but significant improvement.

01:12:15.560 | But again, in most cases,

01:12:17.640 | nicotine is just simply not going to improve physical output

01:12:21.240 | if it's delivered through a smoked cigarette,

01:12:24.920 | through vaping, through dipping, or through snuffing.

01:12:27.780 | So if all these behaviors are terrible

01:12:29.840 | for essentially every aspect of our health, frankly,

01:12:32.480 | I mean, when you look at the literature,

01:12:33.400 | it's terrible for pregnant women, it's terrible for kids,

01:12:35.620 | it's terrible for older people,

01:12:37.340 | it's terrible for younger people.

01:12:38.860 | I mean, you really cannot find a scenario

01:12:40.840 | in which smoking, vaping, dipping, or snuffing

01:12:43.820 | are good for us,

01:12:44.920 | and yet people like the effects on the brain

01:12:47.320 | and they feel quite addicted to them,

01:12:49.540 | even if they say they're not.

01:12:50.920 | Most of those people would be unwilling

01:12:52.700 | to give up their practice of nicotine delivery

01:12:56.900 | for more than a few hours.

01:12:58.100 | In fact, if you look at the effects of withdrawal,

01:13:00.080 | and we are going to talk about

01:13:01.060 | what withdrawal of nicotine looks like,

01:13:03.720 | what you find is that as soon as four hours

01:13:07.540 | after the last ingestion of nicotine

01:13:09.880 | by way of cigarette or vaping or dipping or snuffing,

01:13:13.420 | what people start to experience is some agitation,

01:13:16.320 | craving for nicotine, of course,

01:13:18.240 | and while craving is kind of a vague concept,

01:13:20.820 | it's actually a very specific biological mechanism,

01:13:23.360 | it's the drop in dopamine that's starting to occur,

01:13:26.840 | so much so that there's a drop in dopamine below baseline,

01:13:29.980 | that is the increase in dopamine

01:13:31.920 | that would normally be experienced

01:13:33.800 | from smoking, vaping, dipping, or snuffing

01:13:36.420 | is now not happening,

01:13:37.980 | and in fact, the levels of dopamine are dropping

01:13:40.180 | below where they would have been

01:13:41.620 | even without performing that behavior.

01:13:44.520 | So that's what craving is,

01:13:46.780 | and withdrawal is an increased sense of that craving

01:13:50.180 | as well as a lot of negative stuff like stomach aches

01:13:52.500 | or nausea or irritability

01:13:54.900 | and often collections of all of those.

01:13:56.960 | So because these nicotine delivery approaches

01:13:58.880 | are so terrible for our health,

01:14:01.100 | and also because as many as 70% of people who smoke

01:14:06.020 | would like to quit but either feel they can't

01:14:08.340 | because they've tried and failed repeatedly often,

01:14:11.260 | or because it's just too scary,

01:14:13.200 | meaning the reinforcing properties are too strong

01:14:15.380 | and therefore they can't imagine living without them,

01:14:18.260 | or the withdrawal effects are too strong

01:14:20.960 | and they can't imagine living with those,

01:14:23.720 | well then is there hope for quitting smoking,

01:14:26.940 | vaping, snuffing, or dipping?

01:14:29.300 | And the short answer fortunately is yes,

01:14:31.880 | there are excellent ways to do that,

01:14:33.320 | and some of them are single event treatments,

01:14:36.900 | and we're going to talk about those shortly.

01:14:39.500 | But before we do that,

01:14:40.360 | I want to highlight one very brief point,

01:14:42.460 | which is that nicotine is not the cause of cancer,

01:14:46.580 | nicotine is not the carcinogen,

01:14:48.700 | it's the other things in tobacco

01:14:52.100 | or associated with the nicotine delivery device

01:14:55.820 | that are causing cancer,

01:14:57.360 | and I should mention the other negative impacts

01:15:00.500 | on our health in particular

01:15:02.060 | by way of disrupted endothelial blood vessel function.

01:15:06.060 | Now that leads us to this issue of vaping,

01:15:07.900 | because as many of you know and probably are thinking,

01:15:11.040 | as I've been delivering this information,

01:15:13.900 | people don't vape tobacco,

01:15:16.740 | the way that vaping pens are designed

01:15:19.140 | is that it includes some liquid, it involves heat,

01:15:22.740 | and it does not involve the burning off of tobacco.

01:15:25.620 | In fact, there's a constant updating

01:15:28.660 | of the engineering of these vape pens

01:15:30.900 | so that they can be very low heat,

01:15:33.140 | in some cases they use even non-heating approaches

01:15:37.260 | to vaporize the nicotine

01:15:39.040 | and allow it to enter the bloodstream very quickly.

01:15:42.580 | I must say, in a lot of ways,

01:15:44.100 | vaping resembles crack cocaine.

01:15:47.720 | The reason why vaping and crack cocaine are so similar

01:15:51.140 | is the speed of entry of nicotine into the bloodstream.

01:15:55.120 | This isn't an episode about cocaine,

01:15:57.380 | but I just want to very briefly touch

01:15:59.300 | on some of the delivery routes for cocaine,

01:16:01.300 | because they parallel a lot of the delivery routes

01:16:04.100 | for nicotine, and we can learn a lot

01:16:06.340 | about drug pharmacokinetics and dopamine

01:16:09.600 | if we look at the parallels between cocaine and nicotine.

01:16:13.200 | I'll preface this by saying cocaine is a terrible drug.

01:16:18.320 | It is actually a schedule two drug in the United States,

01:16:21.140 | which means that it has a very, very limited,

01:16:23.760 | yet still present medical application,

01:16:25.980 | mainly as an anesthetic in certain laboratory

01:16:29.680 | and hospital conditions.

01:16:31.500 | But aside from that, it's very clear

01:16:33.680 | that cocaine is one of the most debilitating drugs

01:16:35.820 | that humans can use because of the way

01:16:37.800 | that it impacts the dopamine system.

01:16:39.620 | And it basically creates a loop whereby the only thing

01:16:43.140 | that can really trigger dopamine release is cocaine.

01:16:46.860 | And as I've said before, the way that I define addiction

01:16:50.200 | is it's a progressive narrowing of the things

01:16:52.260 | that bring people pleasure.

01:16:53.300 | Cocaine certainly falls into the category

01:16:55.400 | of addictive drugs, strongly addictive drugs.

01:16:58.700 | And in fact, it has the additionally pernicious feature

01:17:01.540 | that after using cocaine for some period of time,

01:17:04.860 | the amount of dopamine that's released

01:17:06.520 | becomes progressively lower and lower and lower

01:17:08.920 | so that people can never get back to a state

01:17:10.980 | in which dopamine release is ever as great as it was

01:17:14.420 | the first time they did cocaine or prior to doing cocaine.

01:17:17.620 | Now, with a long period of no cocaine use whatsoever

01:17:22.620 | and protecting the dopamine system

01:17:25.820 | in a number of different ways,

01:17:27.380 | people can often, not always,

01:17:29.860 | but often recover their dopamine system,

01:17:32.700 | if not completely, then near completely.

01:17:35.220 | So by all means, if you have a problem with cocaine,

01:17:38.560 | quit, find a way to quit, get treatment,

01:17:41.100 | get over that one way or another.

01:17:42.760 | We have an episode with an expert guest, Dr. Anna Lemke,

01:17:46.280 | who's a physician and the chief

01:17:47.900 | of the Stanford School of Medicine

01:17:49.540 | Dual Diagnosis Addiction Clinic.

01:17:51.700 | She's a world expert in dopamine and addictive substances

01:17:54.760 | and addictions of all kinds.

01:17:56.180 | You can find that episode at Hubermanlab.com.

01:17:58.460 | It's filled with information about how to get over

01:18:01.020 | different types of addictions, including cocaine addiction.

01:18:03.120 | Also check out her absolutely phenomenal

01:18:05.320 | and indeed important book, "Dopamine Nation,"

01:18:07.200 | which touches on some of this as well.

01:18:09.680 | And in the show note captions for the episode

01:18:11.980 | where Dr. Lemke was my guest,

01:18:14.120 | you can also find some additional resources

01:18:15.760 | related to that.

01:18:16.600 | So cocaine is terrible, that needs to be acknowledged.

01:18:19.320 | It should be avoided and you should find a way to quit it

01:18:21.780 | if you are currently using.

01:18:23.240 | With that said, the delivery mechanism for cocaine

01:18:27.580 | strongly parallels the delivery mechanisms for nicotine.

01:18:30.900 | That is, people will snort cocaine,

01:18:32.600 | which is a lot like snuffing or dipping.

01:18:34.720 | That is, when people snort cocaine,

01:18:36.260 | they're bringing cocaine into proximity or into contact

01:18:38.780 | really with the mucosal lining of the nasal passages,

01:18:41.820 | which then allows the psychoactive substances

01:18:44.620 | to permeate into the bloodstream.

01:18:46.960 | Very seldom do people eat it,

01:18:49.100 | although that does happen from time to time.

01:18:52.100 | People will inject it as so-called mainlining,

01:18:55.060 | which is a very rapid entry into the bloodstream

01:18:57.040 | because it's direct application to the bloodstream

01:18:59.680 | by way of injection.

01:19:00.780 | And then there's crack cocaine,

01:19:02.280 | which is essentially like a vaporizing of the cocaine

01:19:05.140 | from a so-called cocaine rock.

01:19:07.660 | That somewhat resembles vaping of nicotine.

01:19:12.660 | So while the vape pen involves a liquid

01:19:15.360 | that sold a cartridge that contains nicotine

01:19:17.740 | and often other flavors as well,

01:19:20.340 | flavorings, I should say,

01:19:21.820 | both crack cocaine and vaping cause very rapid increases

01:19:27.860 | in the relative substances that are psychoactive.

01:19:29.900 | In the case of cocaine, that would be cocaine.

01:19:32.100 | And the increase in dopamine in the brain and body,

01:19:34.880 | I should mention.

01:19:35.720 | And in the case of vaping,

01:19:37.060 | there's a very rapid increase in blood concentrations

01:19:39.780 | of nicotine, much faster than occur with cigarette smoking

01:19:43.340 | or other modes of nicotine delivery.

01:19:45.780 | So that speed of onset turns out to be a critical parameter

01:19:49.760 | because the speed of onset of nicotine

01:19:52.520 | is going to also determine the speed of release of dopamine

01:19:56.100 | in the nucleus accumbens and ventral tegmental area,

01:19:58.180 | that mesolimbic reward pathway.

01:20:00.520 | And with the mesolimbic reward pathway,

01:20:02.180 | it's not just about the peak,

01:20:04.440 | meaning the maximal amount of dopamine that's released,

01:20:08.200 | but it's the time course, how steep the curve is,

01:20:11.020 | how quickly that dopamine increases,

01:20:12.680 | that's going to determine how reinforcing,

01:20:15.180 | how habit forming and indeed how addictive

01:20:17.560 | a particular substance is.

01:20:19.380 | So one of the major important differences

01:20:21.600 | between vaping and cigarette smoking

01:20:23.400 | is that the onset of dopamine release from vaping is faster.

01:20:27.600 | And even a subtle increase in the rate

01:20:30.420 | at which dopamine increases in the mesolimbic reward pathway

01:20:33.860 | can make a given amount of nicotine

01:20:37.180 | much more habit forming and addictive.

01:20:40.780 | This probably explains the fact that many, many more people

01:20:44.580 | in particular young people, age 25 and younger,

01:20:47.300 | are vaping at phenomenal rates now.

01:20:50.300 | People are starting to vape in just about everywhere.

01:20:52.780 | You see this in restaurants, you see it on the street.

01:20:54.740 | Indeed, you even see it in the classroom.

01:20:57.220 | This has actually become sort of sport of sports.

01:21:00.300 | It's certainly not something I encourage.

01:21:02.020 | In fact, when I learned about this from a college student,

01:21:05.000 | new college student,

01:21:06.220 | is telling me that many college students

01:21:08.180 | are actually bringing vape pens into the classroom.

01:21:10.020 | I think this is also happening in high schools

01:21:11.840 | and even junior high schools.

01:21:13.800 | This is a really concerning practice.

01:21:16.560 | And here, I'm not trying to come across as the,

01:21:18.500 | you know, the anti-vaping crusader,

01:21:20.040 | but I must say given the negative effects

01:21:22.520 | on one's health in the longterm,

01:21:24.280 | but also given these exceedingly powerful reward properties

01:21:28.040 | of nicotine entering the bloodstream quickly

01:21:30.760 | and dopamine being released very quickly

01:21:33.340 | from the mesolimbic reward pathway,

01:21:35.680 | what we're seeing out there makes total sense.

01:21:38.320 | Young people's brains are essentially getting wired

01:21:42.000 | to the expectation that dopamine

01:21:44.160 | is going to be increased dramatically and quickly

01:21:47.140 | under their control, except it's under their control

01:21:50.100 | only in a very narrow set of circumstances.

01:21:52.480 | Recall the definition of addiction,

01:21:54.320 | a progressive narrowing of the things

01:21:56.320 | that bring you pleasure.

01:21:57.160 | We can change that statement to also say

01:22:01.000 | a progressive narrowing and specific kinetics,

01:22:05.100 | that is specific time course

01:22:07.480 | of the things that bring you pleasure.

01:22:09.160 | Now that's a bit of a nerdier statement

01:22:10.800 | than a progressive narrowing

01:22:11.680 | of the things that bring you pleasure.

01:22:12.700 | But what we're going to see in the next few years, I believe,

01:22:16.560 | is an entire generation of young people

01:22:19.000 | for which a very large percentage of them

01:22:21.880 | are going to be seeking out a pattern or feeling,

01:22:25.520 | because to the person taking it,

01:22:26.680 | they're not looking at their dopamine levels

01:22:28.200 | rising in their blood,

01:22:29.280 | they're experiencing this as an increase in focus,

01:22:31.320 | an increase in alertness, an increase in mood and wellbeing

01:22:34.340 | that is very rapid, very dramatic,

01:22:37.360 | and that simply cannot be recreated by any other substance.

01:22:41.960 | And that's a very concerning scenario,

01:22:44.540 | concerning because that mesolimbic reward pathway

01:22:47.600 | is the only pathway, the only pathway

01:22:51.000 | by which you can achieve the rewarding properties

01:22:53.620 | of any kind of endeavor, not just vaping, of course,

01:22:57.900 | it is the way in which people achieve satisfaction

01:23:00.280 | from reaching a relationship goal or an athletic goal

01:23:04.000 | or an educational goal, any kind of goal

01:23:06.920 | or sense of satisfaction.

01:23:08.160 | And so it comes as no surprise

01:23:10.360 | that vaping is strongly associated

01:23:12.620 | with increased levels of depression,

01:23:14.440 | especially when vaping use drops off.

01:23:16.560 | Why would that be?

01:23:17.440 | If people are getting so much more dopamine

01:23:19.260 | so much more quickly from vaping,

01:23:20.660 | shouldn't they be feeling better?

01:23:22.520 | That brings us back to the critical,

01:23:24.860 | and I should say defining feature

01:23:26.520 | of the dopamine reward pathway for motivation and wellbeing,

01:23:29.860 | which is that initially a given substance will cause,

01:23:33.080 | let's say an eight out of 10, again, arbitrary units,

01:23:35.920 | but eight out of 10 increase in dopamine,

01:23:39.100 | but with repeated use, what ends up happening

01:23:41.740 | is that even at similar or higher levels of ingestion,

01:23:45.280 | so not just one inhalation a minute,

01:23:47.360 | but maybe two inhalations a minute

01:23:49.060 | or inhalation every 30 seconds,

01:23:51.520 | now it's level four out of 10 activation of dopamine

01:23:54.660 | and then three and then two,

01:23:55.760 | and eventually it drops below baseline.

01:23:58.040 | Now the whole system can be recovered by abstinence

01:24:00.280 | from nicotine consumption,

01:24:02.740 | but the dopamine system is applied to everything,

01:24:04.960 | all sense of wellbeing, all sense of motivation.

01:24:07.600 | So during the period in which one is abstaining

01:24:10.300 | from nicotine and vaping in particular,

01:24:12.800 | people do not feel good, they feel miserable.

01:24:15.960 | That's why it's called withdrawal.

01:24:17.120 | It's associated with a bunch of psychological

01:24:20.420 | and physiological symptoms that all lead back

01:24:24.020 | to trying to get to the same levels of dopamine release

01:24:27.560 | in the same patterns that were experienced

01:24:29.900 | when one initially started vaping.

01:24:32.160 | So I'm not trying to paint a dark picture here,

01:24:33.960 | but frankly, the picture is very dark.

01:24:36.600 | I'm very concerned about a practice of ingesting something

01:24:40.320 | that powerfully modulates the dopamine system

01:24:42.800 | with the sorts of kinetics that one sees

01:24:44.480 | from ingestion of crack cocaine in young people

01:24:46.800 | that has all these other negative health effects

01:24:48.860 | that in the short term is very powerfully rewarding,

01:24:51.280 | increased focus, wellbeing, et cetera,

01:24:53.440 | but that over a very brief period of time

01:24:56.320 | leads to a state in which the entire dopamine reward system

01:25:00.780 | is impaired and can become permanently impaired

01:25:03.800 | unless one intervenes in a very deliberate way.

01:25:06.840 | So people are directly controlling the rate of dopamine

01:25:09.960 | and the frequency of dopamine release

01:25:12.080 | by the duration and frequency of inhalations

01:25:15.440 | off the vape pen.

01:25:16.760 | And that's an incredible thing because what it does

01:25:19.960 | is it sets up the mesolimbic reward pathway

01:25:22.280 | for an expectation that dopamine will be delivered

01:25:24.840 | on that schedule.

01:25:26.560 | So that's one of the things that makes vaping in particular

01:25:30.320 | so hard to quit.

01:25:32.400 | Vaping is actually harder to quit than cigarette smoking

01:25:35.960 | for most people.

01:25:37.880 | Now, does that mean that cigarette smoking

01:25:39.520 | is fairly easy to quit for most people?

01:25:41.920 | No, 70% of people who smoke cigarettes

01:25:45.040 | report that they would like to quit

01:25:46.520 | if they thought they could.

01:25:48.860 | The success rate of quitting smoking

01:25:51.120 | when people try to go just cold turkey,

01:25:53.120 | just quit with no assistance whatsoever,

01:25:54.880 | they might tell their family and friends,

01:25:56.220 | hey, I'm quitting, that's it, is exceedingly low.

01:25:59.360 | It's 5%.

01:26:01.360 | So 5% of the people that say, that's it,

01:26:04.820 | I'm not smoking again, despite cancer diagnosis,

01:26:08.220 | I'm not smoking again,

01:26:09.060 | despite the fear of the negative health effects,

01:26:10.660 | I'm not going to ever smoke again,

01:26:12.640 | despite the financial costs, the health costs.

01:26:16.080 | I mean, I could list off the huge number of things

01:26:18.240 | that it does that are negative,

01:26:19.080 | but you already know these, or you've heard them,

01:26:21.160 | it makes your skin worse.

01:26:22.960 | As I mentioned, it lowers libido, it disrupts hormones,

01:26:26.840 | it disrupts vascular function, brain function,

01:26:30.600 | it does all these terrible things,

01:26:31.800 | and yet most people who try and quit simply can't.

01:26:34.240 | And of the 5% that succeed in quitting,

01:26:36.940 | a full 65% of them relapse within a year.

01:26:40.540 | So that's a very depressing picture,

01:26:42.860 | but it's not to say that people cannot quit,

01:26:45.000 | and in fact, they can.

01:26:45.940 | There are a couple of methods that have been shown

01:26:47.480 | to help people quit.

01:26:49.420 | Some are behavioral and some are pharmacologic.

01:26:53.040 | I just want to touch on the behavioral ones first,

01:26:55.380 | because it turns out that there's a quite powerful method

01:26:58.820 | for quitting nicotine ingestion by way of cigarette smoking,

01:27:02.740 | which also carries over to vaping.

01:27:04.720 | This is beautiful work that's been done by my colleague,

01:27:07.460 | in fact, close collaborator,

01:27:08.740 | although I was not involved in the research

01:27:10.220 | that I'm about to describe, at Stanford,

01:27:12.160 | and his name is Dr. David Spiegel.

01:27:14.340 | He is our associate chair of psychiatry.

01:27:16.540 | He's been a guest on the Huberman Lab Podcast,

01:27:18.500 | and he is a world expert, if not the world expert,

01:27:21.780 | in the clinical applications of hypnosis.

01:27:24.120 | Now, when I say hypnosis,

01:27:25.240 | a lot of people think stage hypnosis,

01:27:26.980 | which is the hypnotist trying to get people

01:27:28.540 | to do certain things and say certain things,

01:27:30.920 | not necessarily against their will,

01:27:32.920 | because they actually have to agree,

01:27:34.120 | but the hypnotist is dictating

01:27:35.980 | what the person thinks, says, and does.

01:27:38.860 | Clinical hypnosis is vastly different from that.

01:27:41.860 | Clinical hypnosis is where the person, the patient,

01:27:44.980 | actually directs their own brain changes

01:27:47.860 | toward a specific emotional or behavioral goal.

01:27:51.120 | Work from Dr. David Spiegel's laboratory, done in 1993,

01:27:55.340 | but that now has been repeated many, many times,

01:27:57.620 | and has carried over into some more modern studies,

01:27:59.460 | and I'll provide links to those studies

01:28:01.920 | in the show note caption so that you can access them.

01:28:04.740 | Those studies have shown

01:28:06.000 | that using a specific form of hypnosis,

01:28:08.900 | people can achieve complete and total cessation

01:28:13.940 | of cigarette smoking,

01:28:15.680 | and there's no reason to believe

01:28:16.760 | this doesn't also carry over to vaping

01:28:19.060 | through one single hypnosis session,

01:28:21.740 | and the success rates are incredibly high

01:28:24.360 | when one considers that normally

01:28:25.800 | it would be only a 5% success rate.

01:28:28.260 | The success rate with this particular hypnosis

01:28:30.420 | developed at Stanford School of Medicine

01:28:32.280 | by Dr. David Spiegel is 23% of people

01:28:35.900 | who do this hypnosis one time succeed in quitting smoking.

01:28:39.600 | Now, in the old days, which actually wasn't that long ago,

01:28:43.580 | before the advent of smartphones

01:28:45.700 | and before the internet took off

01:28:47.740 | to the extent that it has now,

01:28:49.340 | this was done by having someone come into the clinic

01:28:52.700 | and Dr. Spiegel himself or one of his colleagues

01:28:55.300 | would take somebody through the hypnosis.

01:28:57.300 | Nowadays, you can access this hypnosis.

01:29:00.580 | There's a wonderful app

01:29:02.140 | that was developed by Dr. David Spiegel and others.

01:29:05.240 | It's called Reveri, R-E-V-E-R-I.

01:29:07.820 | I've talked about this app a few times on the podcast before

01:29:10.000 | because there are hypnosis scripts within the app

01:29:12.280 | for enhancing sleep, for improving ability to fall asleep

01:29:14.900 | if you wake up in the middle of the night,

01:29:16.480 | for focus and a number of other

01:29:18.160 | behavioral and emotional changes.

01:29:20.520 | There's also a function in the Reveri app

01:29:23.000 | for smoking cessation,

01:29:24.660 | which exactly parallels the sort of in laboratory

01:29:28.880 | and in clinic approaches that Dr. Spiegel would use

01:29:31.940 | were you to show up at his clinic or in his laboratory,

01:29:34.420 | and since that's not possible

01:29:35.900 | for the large number of people out there,

01:29:37.860 | if you or somebody else is trying to quit smoking

01:29:40.740 | or vaping or dipping or snuffing for that matter,

01:29:45.140 | I strongly encourage you to check out the Reveri app.

01:29:47.820 | You can find it easily by going to reveri.com.

01:29:50.780 | It's available in various formats.

01:29:52.660 | Some of it is available free, some of it is behind a paywall,

01:29:55.580 | but given the tremendously negative impact

01:29:57.900 | of smoking, vaping, dipping, and snuffing,

01:30:01.260 | the hypnosis for smoking cessation that Reveri has

01:30:05.380 | seems at least to me

01:30:07.040 | as a very powerful and worthwhile resource.

01:30:09.580 | So please check that out

01:30:10.580 | if you're somebody who's trying to quit ingesting nicotine

01:30:13.860 | by any of the four methods that I just described.

01:30:16.600 | Now, of course, there are other methods

01:30:17.760 | that people have used to successfully quit smoking or vaping

01:30:20.260 | or other forms of nicotine delivery.

01:30:22.980 | And there's actually an excellent review on this topic.

01:30:25.380 | So before diving into a few of the specifics

01:30:27.240 | about some of the pharmacology of using nicotine itself

01:30:31.220 | to quit smoking or nicotine itself to quit vaping,

01:30:34.060 | or the use of various things, even SSRIs, antidepressants,

01:30:38.100 | to quit smoking or vaping,

01:30:40.340 | I just want to point you to a review article

01:30:42.080 | that if you'd like to get a complete survey

01:30:43.680 | of all the options that are available,

01:30:45.620 | there's an excellent review on this.

01:30:47.700 | It was published just a couple of years ago in 2020.

01:30:50.180 | The title of the article is "Pharmacologic Approach

01:30:52.620 | to Smoking Cessation,

01:30:53.860 | an Updated Review for Daily Clinical Practice."

01:30:56.540 | And even though this is mainly focused on smoking cessation,

01:30:59.840 | it carries over quite nicely to vaping.

01:31:02.380 | And it details a number of statistics.

01:31:04.260 | The fact that every year 700,000 or more people die

01:31:07.460 | because of smoking-related diseases.

01:31:08.940 | So there again, you have the negative health effects

01:31:11.980 | that younger people are smoking,

01:31:13.340 | that women are smoking more nowadays,

01:31:14.940 | and that even though you see less smoking,

01:31:16.360 | typically in the US and Canada,

01:31:17.980 | and even in Northern Europe, some places,

01:31:19.900 | there's still many, many people are smoking

01:31:21.380 | who would like to quit.

01:31:22.660 | But that 75% of people,

01:31:24.800 | at least according to this review earlier, I said 70%,

01:31:26.980 | but estimates are as high as 75% of people

01:31:29.620 | who try to quit smoking relapse within the first week.

01:31:32.720 | The first week, they just go right back to it.

01:31:34.260 | That's how powerfully reinforcing the nicotine is.

01:31:36.780 | Remember, it's the nicotine in the cigarette

01:31:38.680 | that's powerfully reinforcing,

01:31:39.880 | but it's also the oral habit, the motor habit.

01:31:44.880 | There is this thing about density of sensory receptors

01:31:47.780 | in the lips.

01:31:48.620 | People like bringing things to their lips.

01:31:50.580 | Food, cigarettes, other lips in some cases, et cetera.

01:31:56.460 | There is a reinforcement pathway related to that

01:31:58.960 | for sort of obvious adaptive reasons.

01:32:01.440 | And as a consequence,

01:32:03.940 | there is a reinforcement both from the behavior

01:32:06.560 | and from the dopamine released from the nicotine itself.

01:32:09.140 | And as I mentioned earlier,

01:32:10.520 | from the positive reinforcement

01:32:12.680 | that comes from increased focus,

01:32:13.920 | so the money that you make through work

01:32:15.240 | or your attentional ability,

01:32:16.640 | or the fact that you're alert and people feel you present,

01:32:18.600 | all of that funnels back into positive reinforcement,

01:32:21.860 | behavioral reinforcement,

01:32:23.760 | and then what we would call addiction.

01:32:26.240 | So this review covers all of that.

01:32:28.520 | And then steps beautifully

01:32:30.220 | through nicotine replacement therapy and various compounds,

01:32:33.760 | several of which I'm going to talk about now,

01:32:35.740 | which have been shown to increase that number

01:32:37.980 | that we talked about earlier of only 5% of people

01:32:40.620 | who try to quit with no other support,

01:32:43.080 | pharmacologic or hypnosis or otherwise,

01:32:44.880 | just say, that's it, I'm not going to smoke again,

01:32:47.040 | or I'm not going to vape again.

01:32:48.680 | Only 5% of people succeed in doing that.

01:32:50.880 | And even among those, many end up relapsing later.

01:32:53.760 | There are a couple of pharmacologic approaches.

01:32:55.860 | One of the main ones that's received a lot of attention

01:32:57.800 | in recent years is Bupriperone,

01:33:00.080 | sometimes referred to by its commercial name, Wellbutrin.

01:33:04.080 | Now, Bupriperone is a compound

01:33:07.800 | that increases the release of dopamine

01:33:10.020 | and to a lesser extent, epinephrine,

01:33:11.900 | and some other neurochemicals as well.

01:33:13.600 | It's used for the treatment of depression

01:33:15.600 | and for smoking cessation.

01:33:17.720 | Now, I want to point out again, I'm not a psychiatrist,

01:33:19.920 | so I'm not telling you to take Bupriperone,

01:33:22.120 | AKA Wellbutrin, but I'm going to give you a little bit

01:33:24.520 | of the contour of what's typically done

01:33:26.640 | in terms of Bupriperone administration

01:33:28.460 | to help people get relief

01:33:30.360 | from some of the withdrawal symptoms

01:33:32.240 | of trying to quit smoking or vaping

01:33:33.900 | or other forms of nicotine ingestion.

01:33:36.540 | Typically, Bupriperone is taken

01:33:38.780 | in 300 milligram per day doses

01:33:41.440 | divided into two dosages of 150 milligrams each,

01:33:44.160 | or sometimes there's a slow release formula.

01:33:47.200 | The dosages will vary from person to person.

01:33:49.900 | I want to really emphasize

01:33:51.400 | that there is an increased seizure risk with Bupriperone.

01:33:54.640 | It only occurs in a small fraction of the population,

01:33:56.940 | but nonetheless is a real concern

01:33:58.960 | for those members of the population.

01:34:00.380 | So for those of you with seizure risk,

01:34:02.220 | whether you know it or not,

01:34:03.620 | that's going to be a valid concern

01:34:06.120 | in terms of potential side effects.

01:34:07.960 | The other thing about Bupriperone is that it has to be used

01:34:11.720 | with caution in patients that have liver disease

01:34:13.720 | or renal disease that can impact the amount

01:34:16.600 | that anyone can take,

01:34:17.440 | meaning sometimes people have to take a much lower dose

01:34:19.660 | if they have renal disease or liver disease,

01:34:22.200 | and sometimes they can't take it at all.

01:34:23.900 | Sometimes if people are taking benzodiazepines

01:34:26.240 | for whatever reason or other sedatives,

01:34:28.180 | there are contraindications there.

01:34:29.740 | So Bupriperone isn't a kind of one size fits all

01:34:33.360 | or magic bullet for quitting smoking.

01:34:35.480 | Nonetheless, for people that can take it safely,

01:34:38.040 | and again, this is a prescription drug,

01:34:39.840 | a board certified psychiatrist or other physician

01:34:42.160 | is going to have to prescribe it for you

01:34:43.560 | if it's appropriate for you,

01:34:44.640 | and it moves that number of 5% success rate

01:34:47.440 | to about what one sees with the clinical hypnosis

01:34:50.520 | to about 20% of people will successfully

01:34:55.060 | overcome their nicotine,

01:34:56.780 | or I should say their smoking or vaping addiction.

01:35:00.260 | Now it's important to ask why this would work, right?

01:35:03.080 | I mean, it's not as if Bupriperone

01:35:05.180 | is increasing nicotine per se.

01:35:08.180 | What it's doing is it's tapping

01:35:09.540 | on that mesolimbic reward pathway, increasing dopamine,

01:35:12.300 | or at least allowing dopamine levels

01:35:13.780 | to stay substantially elevated enough

01:35:16.560 | that people don't experience some of the drop in dopamine

01:35:19.880 | that leads to the withdrawal symptoms,

01:35:21.380 | the lessening of mood, et cetera,

01:35:22.840 | and it's no coincidence that Bupriperone

01:35:24.560 | is also an antidepressant.

01:35:26.400 | It's a common antidepressant

01:35:27.920 | for people that experience negative side effects

01:35:29.720 | with the so-called SSRIs,

01:35:31.240 | the selective serotonin reuptake inhibitors

01:35:33.840 | that prevent them from taking those things

01:35:35.360 | like lessen libido or appetite,

01:35:37.160 | or in some cases increased appetite,

01:35:39.280 | or any number of other side effects that some people,

01:35:41.620 | not all, but some people experience with SSRIs.

01:35:43.720 | They'll be prescribed Wellbutrin, Bupriperone

01:35:46.680 | is the generic name.

01:35:48.160 | So Wellbutrin being the commercial name,

01:35:49.880 | again, Bupriperone is what they'll be prescribed instead.

01:35:53.160 | With the caveats of seizure risk, renal disease,

01:35:57.560 | liver disease, et cetera,

01:35:58.880 | the outcomes with Wellbutrin for smoking cessation

01:36:02.400 | are pretty good.

01:36:03.240 | I mean, if you think about an increase from 5% to 20%,

01:36:05.920 | that's pretty dramatic.

01:36:07.080 | And yet I also want to refer back to the incredible success

01:36:10.320 | of the clinical hypnosis approach.

01:36:12.080 | Again, you can find that at reverie.com.

01:36:14.680 | The clinical hypnosis approach has a success rate

01:36:17.080 | of 23%, so it's very closely aligned with,

01:36:20.740 | if not exceeding the success rate with Bupriperone.

01:36:24.400 | Of course, there are other pharmacologic approaches

01:36:26.560 | to quitting smoking or vaping.

01:36:29.580 | All of them generally circle back to increasing dopamine

01:36:33.020 | and or norepinephrine in order to offset

01:36:35.200 | some of the withdrawal symptoms of smoking sensation

01:36:38.420 | or vaping cessation.

01:36:39.680 | A very common approach for people to try and quit smoking

01:36:42.740 | or vaping is to use nicotine itself to try

01:36:47.420 | and prevent people from seeking nicotine

01:36:49.820 | through a cigarette or a vape pen.

01:36:52.260 | What I mean by that is people using a nicotine patch

01:36:55.220 | or nicotine gum or other nicotine delivery device

01:36:59.060 | that is not cigarettes and not vaping

01:37:01.980 | in order to maintain levels of nicotine

01:37:05.200 | in their bloodstream,

01:37:07.060 | which of course means maintain levels of nicotine

01:37:09.220 | in their brain and body to the same extent

01:37:12.140 | that they would if they were smoking or vaping,

01:37:15.000 | maybe even gradually taking down the total amount

01:37:18.380 | of nicotine in their brain and body by reducing the number

01:37:22.680 | or size of nicotine gum pieces that they ingest each day

01:37:26.380 | or keeping the patch on for a shorter amount of time

01:37:29.000 | or getting a lower dose patch

01:37:30.340 | that releases less nicotine total or over time.

01:37:34.300 | All of those approaches have been shown

01:37:37.180 | to be reasonably successful.

01:37:39.100 | I'll get to the numbers in a few minutes,

01:37:40.160 | but reasonably successful in allowing people

01:37:43.320 | to quit smoking or vaping.

01:37:47.100 | Again, most of the data is on cigarette smoking

01:37:49.740 | because vaping is a relatively new phenomenon,

01:37:52.180 | although quite troublingly,

01:37:54.420 | it's a very rapidly increasing behavior,

01:37:57.780 | especially in the young population.

01:37:59.300 | So that's why I'm kind of lumping these two things together

01:38:01.420 | because I think very soon we are going to need

01:38:05.420 | an all out campaign for how to counter vaping addiction.

01:38:09.540 | So what do we know about smoking sensation

01:38:11.900 | using nicotine itself?

01:38:13.540 | Is the patch best?

01:38:14.780 | Is nicotine gum best?

01:38:16.500 | It turns out that a combination of approaches is best.

01:38:20.500 | So somewhat surprising,

01:38:21.620 | but it was very clear from the literature

01:38:22.820 | that I was able to find that using nicotine patches

01:38:26.160 | for some period of time and then switching to a gum

01:38:29.060 | and then perhaps switching to a nasal spray,

01:38:33.120 | that's going to be the most effective.

01:38:34.940 | Then the question is how long to continue each of those

01:38:38.100 | and whether or not to overlap them.

01:38:39.580 | It seems as if doing one for about a week

01:38:42.080 | and then switching to another for about a week

01:38:43.700 | and then switching to another is one rational

01:38:46.860 | and reasonable approach

01:38:47.780 | that many people have used successfully.

01:38:50.160 | Why would that be?

01:38:51.000 | Well, it all has to do with the different rates

01:38:52.700 | of absorption of nicotine into the bloodstream

01:38:55.380 | and then the downstream consequences of that

01:38:57.740 | on the dopamine, acetylcholine, epinephrine

01:39:00.420 | and other systems of the brain and body.

01:39:02.600 | And while there hasn't been an extremely detailed study

01:39:05.940 | of the exact kinetics of how the nasal sprays

01:39:08.860 | versus the transdermal patches versus the gums, et cetera,

01:39:11.400 | work, there's a logical structure to it

01:39:13.500 | that will immediately make sense to you.

01:39:14.840 | First of all, the transdermal patches

01:39:17.300 | provide a fairly steady state dopamine release

01:39:20.140 | across the day.

01:39:21.380 | And oftentimes people are wearing them at night as well.

01:39:23.740 | This is relevant because if people are ingesting nicotine

01:39:26.800 | by way of smoking and vaping,

01:39:29.300 | hopefully they're not waking up in the middle of the night

01:39:31.900 | just to smoke or vape or believe it or not,

01:39:33.300 | some people do that.

01:39:34.160 | But of course, while people are asleep,

01:39:36.360 | they are not smoking or vaping.

01:39:38.500 | They always tell you don't fall asleep

01:39:39.420 | with a cigarette in your mouth.

01:39:40.260 | You burn the whole house down.

01:39:42.300 | But exceedingly rare to have people

01:39:45.460 | who are smoking in their sleep.

01:39:46.980 | So people wake up in the morning

01:39:48.580 | and because the half-life of nicotine from smoking or vaping

01:39:51.540 | is very short, anywhere from one to two hours,

01:39:54.000 | they are essentially in a state of withdrawal

01:39:55.620 | at the point where they wake up in the morning.

01:39:56.980 | How can I say that?

01:39:57.820 | Well, remember withdrawal sets in about four hours

01:40:00.420 | after the last ingestion of nicotine by cigarette

01:40:03.160 | or by inhalation from the vape pen.

01:40:05.060 | So people are waking up in nicotine withdrawal

01:40:07.740 | and then immediately going into the behavior

01:40:10.020 | of ingesting nicotine or very soon after waking

01:40:12.060 | for most people.

01:40:13.600 | So nicotine patch is going to be very effective

01:40:16.560 | for a week or so.

01:40:17.620 | Again, talk to your physician

01:40:18.620 | about the best approach for this,

01:40:20.460 | but then switching to a nasal spray

01:40:23.900 | or switching to nicotine gum for about a week,

01:40:26.140 | which is going to change the kinetics

01:40:27.600 | of that nicotine absorption to the bloodstream

01:40:29.700 | and change the release of dopamine

01:40:32.100 | and other neurochemicals within the brain.

01:40:33.760 | That's going to keep the system intentionally off balance

01:40:37.200 | so that it never comes to expect one single pattern

01:40:40.860 | or amplitude of dopamine release.

01:40:44.020 | And that is a very powerful way for a,

01:40:47.660 | let's just call it a quitting method to work

01:40:51.700 | because as I've always said,

01:40:53.320 | the most powerful schedule of dopamine

01:40:56.240 | is going to be this random intermittent reward.

01:40:59.120 | This is what's used in the casinos

01:41:00.860 | in order to take your money.

01:41:02.080 | And generally they do on average,

01:41:03.740 | they take your money more than you take theirs

01:41:06.300 | and they take more of it, not just more often

01:41:09.340 | because they use this random intermittent schedule.

01:41:11.820 | The random intermittent schedule

01:41:13.220 | is one in which you don't really know

01:41:14.860 | when the peaks in dopamine are going to arrive.

01:41:17.300 | And so there isn't this expectation and craving.

01:41:19.780 | And then all of a sudden when dopamine is released,

01:41:21.480 | it's extremely high.

01:41:22.380 | That's how they get you to continue playing,

01:41:23.740 | even though basically you're losing money

01:41:25.320 | and your dopamine is dropping.

01:41:26.340 | They elevate it every once in a while.

01:41:29.220 | Nicotine replacement can be used in a similar way,

01:41:31.740 | but in a benevolent way

01:41:32.880 | in order to help you get over smoking or vaping

01:41:36.260 | by keeping the total amounts of dopamine variable

01:41:39.040 | around the clock.

01:41:40.740 | And by changing the amount of dopamine that's released,

01:41:43.580 | it seems to help people behaviorally and psychologically

01:41:46.960 | because they don't come to expect

01:41:48.380 | having a particular amount of dopamine

01:41:49.900 | in their brain and blood at any given time.

01:41:51.740 | And this is an important point

01:41:53.660 | because it brings us to this notion of homeostasis.

01:41:56.820 | Homeostasis is this tendency for biological systems

01:41:59.480 | to try and reach equilibrium.

01:42:01.120 | What goes up, goes down, et cetera,

01:42:02.540 | and to some extent to the same degree.

01:42:04.820 | So I'll talk about this right now

01:42:05.820 | in the context of nicotine use, withdrawal,

01:42:09.820 | and then the period in which people

01:42:12.280 | no longer crave nicotine.

01:42:14.500 | So you can imagine that if we were to measure

01:42:16.940 | your heart rate, your blood pressure,

01:42:18.460 | and your overall levels of alertness and wellbeing and mood,

01:42:21.260 | let's just give that some value.

01:42:23.080 | Let's say it runs from zero to 10.

01:42:24.700 | Again, arbitrary units.

01:42:25.760 | Let's just take all those physiological measures

01:42:27.980 | and the subjective measure of your mood,

01:42:29.660 | and let's measure it four times an hour across the day,

01:42:33.940 | across the waking hours.

01:42:34.980 | What we would find is a line

01:42:36.080 | that would kind of squiggle a bit.

01:42:37.580 | Maybe a nice text comes in that you really like.

01:42:39.860 | Maybe you get a not so good news

01:42:42.000 | and your kind of autonomic arousal is all over the place.

01:42:45.340 | But on average, it's kind of a squiggly line

01:42:47.500 | where it increases in the morning

01:42:48.800 | 'cause that's typically when body temperature

01:42:50.720 | and autonomic arousal increase.

01:42:52.160 | And then towards the afternoon,

01:42:53.220 | it's going to come sloping down.

01:42:54.260 | And then right before sleep,

01:42:55.100 | there'll be an increase again.

01:42:56.100 | You know, if you've ever felt that,

01:42:56.980 | you kind of run around a lot before sleep,

01:42:58.320 | and then it goes down.

01:42:59.280 | That's kind of the typical contour of autonomic arousal,

01:43:03.220 | mood, et cetera, across the day.

01:43:05.700 | Removing, of course, life events

01:43:07.740 | and things like psychiatric illness

01:43:10.100 | and depression and et cetera,

01:43:12.140 | that's the typical arc of that.

01:43:13.920 | Now let's superimpose on whatever that contour is for you.

01:43:18.020 | Nicotine.

01:43:18.860 | So get a little bolus, as we say,

01:43:21.740 | a little bit of nicotine from smoking a cigarette

01:43:23.940 | or from taking inhalation on a vape pen.

01:43:25.640 | What ends up happening is there's an increase

01:43:27.360 | in blood pressure, increase in heart rate,

01:43:28.760 | increase in mood, increase in alertness,

01:43:30.340 | all the things we talked about earlier.

01:43:32.260 | Over time, the body starts to adjust

01:43:37.180 | so that the baseline upon which that nicotine-induced

01:43:42.180 | increase in arousal would occur is actually reduced, right?

01:43:47.600 | Why would that be?

01:43:48.460 | Well, the body and the brain,

01:43:51.140 | your physiology seeks homeostasis.

01:43:53.020 | So if there's a big increase in all those things

01:43:56.020 | like blood pressure and mood, et cetera,

01:43:57.920 | typically your baseline will drop a little bit

01:44:00.700 | to compensate for that over time after a couple of days

01:44:03.180 | or even weeks of ingesting nicotine.

01:44:05.020 | So let's say you wake up,

01:44:06.140 | you typically take an inhalation off your vape

01:44:08.820 | or you have a cigarette around nine or 10 a.m.

01:44:11.660 | You do that daily.

01:44:13.260 | You get used to a certain level of mood and alertness

01:44:15.700 | and wellbeing for that time of day.

01:44:17.420 | And then if you smoke again in the afternoon, let's say,

01:44:20.120 | you also get accustomed to a certain level of mood

01:44:22.300 | and alertness and wellbeing for that time of day.

01:44:25.020 | Again, it'll vary depending on life events,

01:44:26.820 | but your system sort of gets used to it

01:44:28.440 | and your baseline will drop to compensate for those peaks

01:44:30.980 | so that the peaks aren't quite as high as they were

01:44:33.180 | when you first started using nicotine.

01:44:35.300 | Now you decide to quit.

01:44:36.420 | So now what we're talking about is transitioning

01:44:38.440 | from the consumption

01:44:40.580 | to what we're going to call the withdrawal phase.

01:44:43.100 | Now what happens is you say, "That's it.

01:44:44.600 | I'm going cold turkey.

01:44:46.100 | I know there's only a 5% success rate,

01:44:47.780 | but I'm going to just go cold turkey."

01:44:49.020 | Or somebody will say, "No, I'm going to use the Reverie app."

01:44:51.980 | Or somebody says, "No, I'm going to use buprenorphine

01:44:55.080 | or another method or nicotine patch

01:44:56.920 | or something of that sort."

01:44:57.940 | Well, setting aside the nicotine patch

01:44:59.660 | or the nicotine delivery device

01:45:01.500 | and only focusing on approaches

01:45:04.180 | for getting through withdrawal

01:45:05.860 | that have no direct effects on nicotine, okay?

01:45:09.260 | So not using the nicotine patch,

01:45:10.620 | but say the hypnosis or buprenorphine,

01:45:14.140 | which can increase dopamine,

01:45:15.540 | but it doesn't increase nicotine directly, what happens?

01:45:19.440 | The day that you quit, that homeostatic mechanism

01:45:23.960 | in your brain and body

01:45:25.120 | that sets your level of mood and arousal, et cetera,

01:45:27.900 | does not know and hasn't adjusted to the fact

01:45:30.920 | that you're not bringing in nicotine.

01:45:32.340 | You're not having that cigarette.

01:45:33.420 | You're not having that inhalation on the vape pen.

01:45:35.840 | So what ends up happening is that baseline,

01:45:38.080 | which has been adjusted down to offset the increases

01:45:41.560 | in mood and alertness, et cetera, when you smoke or vape,

01:45:45.960 | is lower than it normally would be.

01:45:48.280 | So that 9 a.m. cigarette time or vape inhalation time

01:45:52.900 | no longer feels above baseline.

01:45:55.420 | It actually feels below baseline

01:45:57.420 | because what you're seeing is the lower amplitude of arousal

01:46:02.420 | that was there to offset the increase you were getting

01:46:05.900 | from vaping or smoking.

01:46:07.220 | And then in the afternoon,

01:46:08.320 | if normally you have a kind of phase of your afternoon

01:46:10.460 | you really enjoy, you go outside,

01:46:11.720 | you have a vape or a cigarette,

01:46:13.460 | you normally are feeling relaxed or you go out at night,

01:46:15.420 | you'd like to vape and you say,

01:46:16.240 | "Nope, I'm not going to do that anymore."

01:46:18.020 | You're going to feel much, much worse

01:46:20.960 | than you would have had you never started smoking or vaping.

01:46:23.380 | Now that's not much help to anyone

01:46:25.900 | who's already started smoking or vaping.

01:46:27.780 | But I say this because it's very important to understand

01:46:30.860 | that the reason why relapse rates are so high

01:46:33.100 | within the first week,

01:46:33.980 | 75% of people relapse within one week

01:46:36.900 | and overall failure rates are 95%,

01:46:39.980 | is because people don't expect to feel even worse

01:46:43.220 | than they did prior to ever smoking or vaping.

01:46:46.060 | So that first week is absolutely critical.

01:46:48.740 | And the beauty of understanding this

01:46:50.220 | is that if you can get through that first week,

01:46:52.580 | either by sheer grit or by finding other methods

01:46:55.860 | to increase dopamine, healthy methods, I would hope,

01:46:58.780 | and certainly cold showers, ice baths

01:47:01.060 | have been shown to do that, by the way.

01:47:03.540 | This was described in Dr. Analemki's book, "Dopamine Nation."

01:47:07.360 | Cold showers can increase dopamine exercise,

01:47:09.500 | positive social interactions.

01:47:11.360 | It's very likely that people will need to use

01:47:13.780 | other healthy methods to offset that reduction in dopamine

01:47:17.140 | if ever they stand to get through that first week.

01:47:19.780 | And again, if you can get through that first week,

01:47:22.340 | chances are quite a bit higher

01:47:24.260 | that you'll be able to maintain

01:47:26.260 | the cessation of smoking or vaping.

01:47:29.100 | And of course, hypnosis, things like buprenparone

01:47:31.980 | can also assist in that.

01:47:33.260 | Buprenparone by way of increasing dopamine pharmacologically,

01:47:36.220 | hypnosis through changes in neural circuitry

01:47:39.100 | that aren't completely understood

01:47:40.340 | but seem to involve a remapping

01:47:42.460 | of some of the so-called default networks

01:47:44.780 | and some of the networks that are involved

01:47:46.380 | in kind of understanding of your own internal state.

01:47:48.880 | This stuff gets a little bit complicated

01:47:50.020 | and we're going to return to this in an upcoming episode

01:47:52.940 | of the "Huberman Lab Podcast."

01:47:54.140 | But there are indeed legitimate changes

01:47:56.840 | in neural circuitry caused by clinical hypnosis

01:47:59.680 | that can at least partially explain why it is so effective

01:48:02.940 | in helping treat or allow people to stop smoking and vaping.

01:48:07.020 | So for those of you out there that either hear

01:48:09.880 | or are saying yourselves, "I just can't seem to quit smoking

01:48:14.500 | or vaping or dipping or snuffing,"

01:48:17.280 | hopefully an understanding

01:48:18.880 | of how that homeostasis process works

01:48:21.280 | and the time course of nicotine,

01:48:23.440 | depending on the delivery device,

01:48:25.160 | hopefully understanding that will allow you

01:48:27.400 | to develop a protocol.

01:48:29.880 | Maybe it involves hypnosis.

01:48:30.960 | Maybe it involves just understanding that the typical times

01:48:33.800 | in which you ingested nicotine

01:48:36.820 | through any of the different approaches

01:48:38.340 | of bringing it into your system

01:48:40.020 | are going to be particularly hard,

01:48:41.300 | but I don't just mean particularly hard.

01:48:43.160 | I mean particularly hard

01:48:44.000 | and you're going to need to do something specific

01:48:46.080 | to offset that decrease in overall autonomic arousal

01:48:50.520 | and dopamine, et cetera.

01:48:52.160 | Hopefully an understanding of that will allow you

01:48:53.880 | to get through that first week.

01:48:55.020 | And if you can make it past that first week,

01:48:56.880 | you stand a very good chance of never going back.

01:48:59.700 | However, I did consult with Dr. David Spiegel

01:49:02.420 | in anticipation of this episode.

01:49:04.340 | Regardless of the method that you used to quit smoking

01:49:08.480 | or vaping, snuffing or dipping,

01:49:10.900 | there's good evidence that a routine maybe once a month

01:49:16.560 | or even once a week hypnosis type approach

01:49:20.800 | to replenish or even enhance the neural circuits

01:49:23.480 | that are allowing you to stay away from nicotine

01:49:25.640 | is going to be a very good idea.

01:49:27.080 | And given that it's a purely behavioral intervention,

01:49:31.400 | I can see no reason as to why people wouldn't want to do that.

01:49:34.000 | Go in and reinforce, tighten the bolts on that circuitry

01:49:36.700 | that are allowing you to not feel the impulse to smoke,

01:49:39.840 | not feel the impulse to vape.

01:49:41.560 | And just a very brief mention,

01:49:43.840 | there is a vast literature on the fact

01:49:46.540 | that when people have quit smoking or vaping

01:49:48.820 | or other form of consuming nicotine,

01:49:51.360 | that when they consume alcohol,

01:49:52.700 | there's a much higher probability of relapse.

01:49:54.340 | There are interactions between alcohol and nicotine

01:49:56.160 | that we'll cover in future episodes.

01:49:57.820 | But for those of you that want to quit,

01:49:59.400 | I want to assure you,

01:50:00.740 | despite the fact that 95% of people fail

01:50:03.400 | with the appropriate tools,

01:50:04.980 | and I like to think with an additional understanding

01:50:07.560 | of the underlying biology and psychology

01:50:09.580 | and what you can expect and when to really dig your heels

01:50:11.880 | and when to reinforce your system with more dopamine

01:50:14.120 | through any of the number of the different protocols

01:50:16.160 | and tools that we've offered here

01:50:17.600 | and that you can find elsewhere

01:50:18.680 | and other episodes of the Huberman Lab Podcast,

01:50:21.200 | I have a high degree of confidence

01:50:22.940 | that you can quit smoking or vaping, dipping or snuffing.

01:50:27.640 | So today, typical of frankly all episodes

01:50:29.820 | of the Huberman Lab Podcast,

01:50:30.840 | we've covered a lot about the biology of a particular system.

01:50:34.680 | We talked about the biology of nicotine in particular.

01:50:38.000 | We talked about vaping and smoking, dipping and snuffing,

01:50:42.120 | and the negative health consequences associated with those.

01:50:45.420 | When I reemphasize that nicotine is not what causes cancer,

01:50:48.860 | it is the delivery device that causes cancer

01:50:51.400 | and the other negative health effects.

01:50:53.440 | That is not to say that people should be ingesting nicotine

01:50:56.440 | through any different methods

01:50:57.360 | simply to get a cognitive boost.

01:50:58.840 | There are certain circumstances

01:51:00.160 | where that might be appropriate for the occasional work bout,

01:51:03.440 | certainly not for physical exercise,

01:51:05.980 | given what we talked about earlier.

01:51:07.640 | But of course, there are more and more approaches

01:51:09.840 | to increasing not just nicotine,

01:51:12.040 | but acetylcholine generally

01:51:13.760 | in order to achieve cognitive enhancement

01:51:15.360 | or physical enhancement,

01:51:16.520 | or I should say physical performance enhancement.

01:51:19.300 | Some of those we talked about earlier, such as alpha-GPC.

01:51:22.000 | In any event, nicotine, it should now be clear,

01:51:25.560 | is an immensely powerful substance,

01:51:27.800 | one of the most commonly ingested substances on the face

01:51:30.480 | of the earth and has been for a very long time.

01:51:32.800 | And now that you understand the underlying biology

01:51:34.820 | and the way in which it changes your psychology

01:51:36.960 | and physiology, that should come as no surprise.

01:51:39.740 | If you're learning from and are enjoying this podcast,

01:51:41.920 | please subscribe to our YouTube channel.

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01:51:53.400 | If you have questions or comments

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01:52:07.200 | That is the best way to support this podcast.

01:52:09.860 | During today's episode and on various previous episodes

01:52:12.400 | of the Huberman Lab podcast, we talk about supplements.

01:52:14.560 | While supplements aren't necessary for everybody,

01:52:16.520 | many people derive tremendous benefit from them

01:52:18.500 | for things like enhancing sleep, hormone function,

01:52:21.600 | focus, and so on.

01:52:22.880 | The Huberman Lab podcast has partnered

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01:52:28.120 | You can find those supplements

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01:53:21.620 | So once again, I'd like to thank you for joining me today

01:53:23.800 | for a discussion about the biology

01:53:25.560 | and psychological effects of nicotine,

01:53:27.440 | this incredibly powerful substance.

01:53:29.200 | And as always, thank you for your interest in science.

01:53:32.260 | [upbeat music]

01:53:34.840 | (upbeat music)

Nicotine’s Effects on the Brain & Body & How to Quit Smoking or Vaping | Huberman Lab Podcast #90

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